1

ivane javaxiSvilis saxelobis Tbilisis saxelmwifo universiteti,

medicinis fakulteti

iv. javaxiSvilis sax. Tsu al. naTiSvilis sax. morfologiis instituti.

klinikuri da eqsperimentuli paTologiis departamenti

xelnaweris uflebiT

irakli lacabiZe

aloqsanuri diabetis dros preparati plaferonis da sinTezuri

radioinertuli androgen meTiltrienolonis zemoqmedebis pirobebSi

pankreasSi mimdinare kompesaciur-adaptaciuri procesebi

disertacia

warmodgenili medicinis doqtoris akademiuri xarisxis mosapoveblad

samecniero xelmZRvaneli:

med.Mmec. doqtori akad.

med.Mmec. doqtori prof. Teimuraz jorbenaZe

konsultantebi:

med. mec. doqtori. T. RvamiCava

med. doqtori. n. didebuliZe

Tbilisi 2015

Nnino javaxiSvili

avtoris stili daculia

2

სარჩევი

შესავალი ........................................................................................................................................ 4

პრაქტიკული ფასეულობა ........................................................................................................ 11

ლიტერატურის მიმოხილვა ..................................................................................................... 12

მასალა და მეთოდები .............................................................................................................. 25

ალოქსანი ................................................................................................................................. 26

პლაფერონი LB ........................................................................................................................ 26

ჰისტოლოგიური კვლევა ....................................................................................................... 26

ელექტრონულ-მიკროსკოპული კვლევა ............................................................................. 27

იმუნოჰისტოქიმიური კვლევა .............................................................................................. 28

ელექტრონul-რადიოავტოგრაფული და რადიოიმუნური კვლევა ............................. 28

სტატისტიკური ანალიზი...................................................................................................... 29

გამოკვლევის შედეგები ............................................................................................................ 30

ვირთაგვების პანკრეასის მორფო-ფუნქციური თავისებურებანი ალოქსანური

დიაბეტის დროს ..................................................................................................................... 30

დანართი 1 ................................................................................................................................... 40

მორფოლოგიური ცვლილებები ვირთაგვების პანკრეასში ალოქსანური დიაბეტის

დროს და პლაფერონის ზემოქმედების შემდეგ ................................................................... 56

დანართი 2 ................................................................................................................................... 60

ალოქსან-პლაფერონის ჯგუფის ვირთაგვების პანკრეასში კუნძულ გარეთ არსებული

იზოლირებული β-უჯრედები და მათი ფუნქციური მდგომარეობის შეფასება

ელექტრონულ-მორფომეტრული მეთოდით ....................................................................... 74

დანართი 3 ................................................................................................................................... 76

ჰორმონალურ-მეტაბოლური ცვლილებები მამრ ვირთაგვებში ალოქსანური

დიაბეტის დროს და სინთეზური რადიოინერტული ანდროგენ მეთილტრიენოლონoს

ზემოქმედების შემდეგ .............................................................................................................. 78

დანართი 4 ................................................................................................................................... 79

გამოკვლევის შედეგების ანალიზი ......................................................................................... 81

3

დასკვნა ....................................................................................................................................... 100

SUMMURY ................................................................................................................................. 104

გამოქვეყნებული შრომების სია ............................................................................................ 107

ლიტერატურა ........................................................................................................................... 108

4

შესავალი

sadReisod, jandacvis aqtualur sakiTxs warmoadgens Saqriani

diabeti, romelic ara marto samedicino problemaa, aramed aqvs didi

socialur-ekonomikuri mniSvneloba, gavrcelebis sixSiris, invalidobis

da sicocxlis xangrZliobis TvalTaxedviT, ara marto saqarTveloSi,

aramed msoflioSi.

mravalricxovani kvlevebi (1-4) eZRvneba am avadmyofobis

epidemiologias, klinikas, morfologias da sikvdilis mizezebs. bolo

wlebis miRwevebma Saqriani diabetis daavadebulTa diagnostikaSi, farTo

dispanserizaciam, axali preparatebis Seqmnam da gamoyenebam

(prolongirebuli insulini da sxva Saqardamwevi saSualebebi), Zireulad

Secvala am avadmyofobis klinikuri mimdinareoba da gazarda sicocxlis

xangrZlioba, Tumca samwuxarod mainc ar SeimCneva am avadmyofobis

klebis tendencia. sxvadasxva qveynebSi Catarebuli kvlevebis safuZvelze

dadgenilia, rom msoflioSi mosaxleobis 2% daavadebulia Saqriani

diabetiT da yovel erT gamovlenil SemTxvevaze modis am avadmyofobis

erTi gamouvleneli forma. e.i. gaaCniaT farulad mimdinare Saqriani

diabeti. mosaxleobis 3% ki aqvs genetikurad ganpirobebuli Saqriani

diabeti. cnobilia, rom mTeli endokrinuli daavadebebis struqturaSi

50% modis Saqrian diabetze (5).

Tanamedrove paTomorfologiis erT-erT mniSvlovan sakiTxs

waრmoadgens qsovilTaSorisi urTierToba. kerZod, parenqima-

mikrocirkulaciuri sistema-SemaerTebeli qsovili - es is kvanZia,

romlis erTiani gaTvaliswinebis gareSe SeuZlebelia viqonioT sruli

warmodgena organizmSi mimdinare paTologiur da adaptaciur

procesebsze.

eqsperimentuli, klinikuri, morfologiuri gamokvlevebis safuZvelze

dadgenilia Saqriani diabetis ganviTarebis paTogenetikuri koncefcia da

gamoyofilia am avadmyofobis ramodenime qvetipi, magram aSkaraa, rom

ZiriTadi mizezi, romelic ganapirobebs daavadebis manifestaciis vadas,

5

daavadebis simZimes pankreasis kunZulebis β-ujredebis dazianebis

xarisxia. swored es gansazRvravs am ujredebis morfologiuri

mdgomareobis Seswavlis interess.

Saqriani diabeti metaboluri da imunuri procesebis moSlis

generalizebuli avadmyofobaa. bolo wlebSi mecnierebis interess

iwvevs Saqriani diabetis zegavlena SemaerTebeli qsovilis

metabolizmze, romelic garda rigi sxva mniSvnelovani funqciebisa

garkveul rols TamaSobs sisxlZarRvis kedlis dazianebis paTogenezSi.

cnobilia, rom pankreasis kunZulebis mikrovaskulაrizaciis ganviTareba

ganpirobebulia urTierTobebiT kunZulebis β-ujredebsa da endoTelur

ujredebs Soris. swored am ujredebis urTierTkavSiriT xdeba

pankreasis kunZulebis mier sekretoruli funqciis uzrunvelyofa.

bolo wlebis monacemebi pankreasis kunZulebis mikrocirkulaciur wreSi

mimdinare cvlilebebze sakmaod qaoturi da winaaRmdegobrivia da aseve

warmoadgens kvlevis mniSvnelovan sagans.

β-ujredebi uSualo kontaqtSi imyofebian pankreasis Aα da δD

ujredebTan, romlebic Tavis mxriv aproducireben glukagons da

somatostatins. Saqriani diabetis sxvadasxva simZimis dros am samive

saxis ujredebis urTierTdamikidebuleba sakmaod rTulia da iTxovs

Semdgom Seswavlas.

Saqriani diabetis dros β-ujredebis proliferacia mniSvnelovnad

CamorCeba maT aRwarmoebas. zemoTqmulidan gamomdinareMmniSvnelovan

Teoriul da praqtikul interess warmoadgens regeneraciuli, aRdgeniTi

procesebis Seswavla pankreasSi am paTologiis pirobebSi. problemis

irgvliv arsebuli informaciis retrospeqtruli analizi (6-9) gviCvenebs,

rom sadReisod gamoikveTa ramodenime aqtualuri sakiTxi. kerZod,

kompensaciur-adaptaciuri procesebis Seswavlisas gansakuTrebuli

yuradReba eniWeba kunZulgareT da kunZulebSi arsebul gardamavali

tipis ujredebs specialuri insulinisaTvis damaxasiaTebeli granulebiT

da Rerovan ujredebs. pasuxis gacemas iTxovs mTeli rigi sakiTxebisa:

saidan warmoiSva es insulinis granulebis Semcveli ujredebi, ra aris

am ujredebis winamorbedebi, rogor xvdeba insulini am ujredebidan

6

sisxlSi, SeiZleba Tu ara, CaiTvalos es ujredebi kompensatorul

gamovlinebad hormonis ukmarisobaze da aris Tu ara am gardamavali

tipis ujredebis gaaqtiurebis SesaZlebloba.

Saqriani diabetis dros gansakuTrebuli yuradReba eTmoba

reproduqciuli hormonebis, kerZod androgenebis monawileobas

pankreasis kunZulebSi mimdinare adaptaciur procesebSi. cvlilebebi

androgenebis metabolizmSi gavlenas axdenen anabolizmis procesebze,

romlebic Tavis mxriv regulirdeba insuliniT da Sesabamisad amZimeben

Saqriani diabetis mimdinareobas. Lliteraturuli monacemebiT (10)

androgen receptorebi monawileobas Rebuloben ujredebSi mimdinare

iseT rTul procesebSi, rogoricaa proliferacia, diferenciacia,

apoptozi. zemoTqmulidan gamomdinare gasagebi xdeba interesi

androgenebis rolisadmi β-ujredebis adaptaciaSi Saqriani diabetis

dros.

Saqriani diabeti qronikulad mimdinare avadmyofobaa, Sesabamisad

pacientebze SeuZlebelia yvela im gamokvlevebis Catareba, romlebic

zustad asaxavs im morfologiur cvlilebebs, romlebic viTardeba

pankreasSi sxvadasxva simZimis Saqriani diabetis dros.

zemoTqmulidan gamomdinare kvlevis mizania aloqsanuri diabetis

eqsperimentul modelze Wistar-is jiSis virTagvebze:

1. Segveswavla უnatifesi morfologiuri cvlilebebi (ujredul da

subujredul doneze), romelic viTardeba pankreasis kunZulebSi

eqsperimentuli diabetiს sxvadasxva simZimis paTologiuri procesis

dros.

2. gamogvevlina is morfologiuri cvlilebebi, romlebic saSualebas

mogvcems ganvsazRvroT dazianebis xarisxi da moculoba raTa Segveqmnas

sruli warmodgena paTologiuri da adaptaciuri procesis

mimdinareobaze aloqsanuri diabetis dros.

3. gangvesazRvra pankreasSi mimdinare regeneraciuli procesebi

aloqsanuri diabetis dros, plaferoniT (amnioturi peptidi) da

sinTezuri radioinertuli androgen- meTiltrienoლონის zemoqmedebis

Semdeg.

7

miRebul monacemebze dayrdnobiT SesaZlebeli iqneba gamovavlinoT

is morfologiuri cvlilebebi, romelic viTardeba pankreasis

kunZulebSi da kunZul gareT aloqsanuri diabetis dros, plaferoniT da

sinTezuri radioinertuli androgen-meTiltrienolონis zemoqmedebis

Semdeg, rac udavod mniSvnelovani iqneba mkurnalobis saTanado da

optimaluri meTodebis SemuSavebisas.

8

კვლევის სიახლე

kvlevis kompleqsuri (histologiuri, იმუნოhistoqimiuri,

bioqimiuri, eleqtronuli, eleqtrono-radioavtografiuli, eleqrono-

morfometriuli da statistikuri) meTodebis gamoyenebiT

Seswavlilia pankreasis kunZulebi, mikrocirkulaციუri sistema,

SemaerTebeli qsovili, aloqsanuri diabetis sxvadasxva simZimis

paTologiuri procesis dros, plaferoniT (amnioturi peptidi) da

sinTezuri radioinertuli androgen-meTiltrienolონis zemoqmedebis

Semdeg.

aRwerilia pankreasis β-ujredebis morfo-funqciuri suraTi

aloqsanuri diabetis ganviTarebis da Camoyalibebis procesSi.

dadgenilia rom es cvlilebebi aris Saqriani diabetis klinikuri

gamovlinebis ZiriTadi morfologiuri maCvenebeli da asaxavs

aloqsanuri diabetis rogorc simZimes, ise stadias. es morfologiuri

maCvenebeli damokidebulia glukozis Semcvelobaze sisxlSi.

gamovlenilia urTierTdamokidebuleba erTis mxriv insulinis

warmomqmnel β-ujredebs da meores mxriv glukagonis da somatostatinis

warmomqmnel Aα da δD ujredebs Soris. dadgenilia, rom aloqsanuri

diabetis dros, pankreasis endokrinuli nawili kompleqsurad pasuxobs

naxSirwylebis cvlis moSlaze mTeli misi komponentebis met-naklebi

monawileobiT.

Ddadgenilia, rom aloqsanuri diabetis dros, pankreasis kunZulebis

mikrocirkulaციურ კალაპოტში ganviTarebul alteraciul cvlilebebs

(endoTelis distrofia, deskvamacia, nekrozi), mosdevs anTebiTi da

imunuri ujredebis migracia transendoTelur perikapilarul sivrceSi

da qsovilebSi, β ujredebis Semdgomi dazianebiT. miRebul monacemebze

dayrdnobiT SeiZleba vivaraudoT, rom β-ujredebis dazianebaSi erT-

erTi mTavari roli miekuTvneba cvlilebebs mikrocirkulaciur

კალაპოტში.Pplaferonis zemoqmedeba aZlierebs endoTelis

proliferacias da xels uwyobs angiogenezis procesis aqtivacias.

9

morfologiuri gamokvlevebi mowmoben rom qsovilovan doneze

moqmedebs meqanizmiebi, romlebic avtomaturad uzrunvelyofen

parenqimisa da stromis urTierTregulacias. paTologiuri procesis

simZimიs proporciulad matulobs mwife fibroblastebis raodenoba,

kunZulebSi Cndeba uxeSi fibrozuli CanarTebi, irRveva pankreasis

kunZulebis struqtura. plaferoniT zemoqmedebis Semdeg aRiniSneba

SemaerTebeli qsovilis rezorbciis procesebis gaZliereba (aseT ubnebSi

Warbadaa makrofagebi). savaraudoa, rom plaferoniT zemoqmedebis Semdeg

aqtiurdeba makrofagebi, romlebic xels uwyoben kolagenuri boWkoebis

liziss.

aloqsanuri diabetis dros gamovlenilia kunZul gareT arsebuli

gardamavali tipis ujredebi β-ujredebis niSan TvisebebiT. dadgenilia,

gardamavali tipis ujredebi SedarebiT metia saSualo simZimis

aloqsanuri diabetis dros da mcirea mZimed mimdinare paTologiuri

procesis SemTxvevaSi, rac dadasturebaa imisa, rom es gardamavali

tipis ujredebi aris kompensatoruli procesis gamovlineba.

kvlevebiT dadgenilia, rom aloqsanuri diabetiT daavadebul

virTagvebis pankreasSi plaferoniT stimulaciis Semdeg gamovlenilia

Rerovani da gardamavali tipis ujredebი, zog ujredeბSi aRiniSneba

CD34, xolo zogSi CK19 mkveTri eqspresia. am ujredebs gaaCniaT maRali

sekretoruli aqtivoba da maTSi naklebad vlindeba destruqciuli

cvlilebebი. ეs ujredebi atareben, rogorc acinaruli, sadinrebis

epiTeluri, pankreasis kunZulSida endokrinuli da mezenqimuri, aseve Bβ-

ujredebis niSan Tvisebebs. miRebuli Sedegebis safuZvelze SeiZleba

vivaraudoT, rom gardamavali tipis ujredebs da Rerovan ujredebs

aqvT potencia neogenezis, diferenciaciis da transdiferenciaciis gziT

diferencirdnen pankreasis β-ujredebSi. amgvarad, rogorc Cans

pankreass stimulaciis Semdeg aqvs unari dasabami misces multipotentur

progenitorebs da Rerovan ujredebs.

kvlevis Sedegad mamr virTagvebSi aloqsanuri diabetis dros

aRiniSneba metaboluri da hormonaluri TviTregulaciis moSla,

romelic vlindeba, rogorc metaboluri stresi. xdeba adaptaciuri

10

hormonebis mniSvnelovani zrda, aromatizaciis procesebis aqtivacia,

testosteronis raodenobis Semcireba, estradiolis raodenobis mateba,

dnm-isa da rnm-is sinTezis Semcireba. sinTezur radioinertuli

androgen-meTiltrienolონis Seyvanis Semdeg sisxlSi glukozis

koncentracia Semcirebulia, adaptaciuri hormonebis koncentracia

miaxloebulia normasTan, klebulobs aromatizaciis procesebis

aqtivacia. aRiniSneba dnm-isa da rnm-is sinTezis zrda, β-ujredebis

proliferaciis mateba. testosteronis miaxloeba normasTan, xels

uwyobs androgenuli receptorebis aqtivacias da organos mdgomareobis

gaumjobesebas.

miRebuli monacemebi saSualebas gvaZlevs viqonioT sruli

warmodgena im paTologiur da adaptaciur procesებze, romlებic

viTardeba pankreasis kunZulebSi, mis parenqimasa da stromaSi

aloqsanuri diabetis sxvadasxva simZimis paTologiuri procesis dros,

preparat plaferoniT da sinTezur radioinertuli androgen-

meTiltrienolონis zemoqmedebis Semdeg.

11

პრაქტიკული ფასეულობა

miRebuli Sedegebi saSualebas gvaZlevs vimsjeloT im cvlilebze,

romlebic viTardeba pankreasSi eqsperimentuli diabetis pirobebSi,

plaferoniT da sinTezuri radioinertuli androgen-meTiltrienolonis

zemoqmedebis Semdeg. miRebuli monacemebi saSualebas gvaZlevs

vivaraudoT analogiuri cvlilebebis ganviTarebaze pacientebis

pankreasSi Saqriani diabetis dros, rogorc am daavadebis aucilebel

komponentze.

aRniSnul monacemebze dayrdnobiT SeiZleba gavakeToT rekomendacia

Saqriani diabetis sxvadasxva simZimis paTologiuri procesis dros

profilaqtikur, Tu samkurnalo RonisZiebebis mizanSewonilobaze da

SevimuSaoT mkurnalobis adeqvaturi meTodebi pankreasis endokrinuli

nawilis potenciuri SesaZleblobis gaTvaliswinebiT.

12

ლიტერატურის მიმოხილვა

E

β-ujredebi yvelaze mravalricxvovania pankreasis kunZulebis

ujredebs Soris, ganlagebulni arian kunZulis centrSi sisxlZarRvebis

garSemo da sxva endokrinul ujredebTan SedarebiT sisxlmomaragebis

TvalsazrisiT priviligirebul mdgomareobaSi imyofebian. β-ujredebis

funqciis daqveiTeba, iseve rogorc maTi raodenobis Semcireba, iwvevs

maT mier gamomuSavebuli hormonis deficits da erT-erT yvelaze

gavrcelebul mZime daavadebas Saqrian diabets (11-14).

histologiuri, eleqtronul-mikroskopuli, morfometruli kvlevebis

safuZvelze eqsperimentuli aloqsanuri diabetis dros Tagvebsa da

virTagvebSi mTeli rigi avtorebის (4, 15-20) mier naCvenebia pankreasis

kunZulebis hipertrofia, maTSi fibrozuli qsovilis kerebis warmoqmniT,

β-ujredebis ricxvis da simkvrivis Semcireba. β-ujredebis

ultrastruqturis Rrma dazianeba, gansakuTrebiT mkveTrad gamoxatuli

cvlilebi maT organelebsa da sekretorul granulebSi. zogierTi β-

ujredebis degranulacia, vakuolizacia, nekrozi. pankreasis kunZulebis

Cveulebrivi struqturis rRvevა.

qronikuli eqsperimentuli aloqsanuri diabetis dros zogi avtorebi

(21, 22) aRniSnaven pankreasis kunZulebis Semcirebas rogorc zomebSi ise

raodenobrivad, wilakTaSoris da acinusebs Soris fibrozs, sustad

gamoxatul limfocitarul infiltracias. atrofirebul kunZulebSi

ujredebis meti nawili Seicavs granulebis mcire raodenobas.

imunohistoqimiuri kvleviT atrofirebul kunZulebSi ujredebi ar

iZlevian reaqcias antiinsulinis da antisomatosatatinis antisxeulebze.

zogierTi nekrozuli kunZuli ganicdis kalcifikacias.

miuxedavad imisa, rom Saqriani diabetis ganviTarebaSi aSkaraa

insulinmaproducirebeli β-ujredebis roli, rigi mkvlevarebis (23-26)

azriT yuradReba unda mieqces agreTve αA da δD ujredebsac, romlebic

13

Sesabamisad gamohyofen hormonebs glukagons da somatostatins. rogorc

Cans am ujredebis reaqcia Saqriani diabetis dros araerTgvarovania,

damokidebulia avadmyofobis stadiaze, paTologiuri procesis simZimeze

da insulinis ukmarisobis xarisxze (27, 28).

H კvlevis histologiuri, imunohistoqimiuri da morfometriuli

meTodebis gamoyenebam eqsperimentuli aloqsanuri diabetis dros

virTagvebSi, SesaZlebeli gaxada avtorebs (23, 25, 28, 29) gamoevlinaT

pankreasis kunZulebSi β, Aα da δD ujredebs Soris arsebuli

urTierTdamokidebulebis aspeqtebi.

avtorebis (24, 30) mier Catarebuli imunohistoqimiuri da

morfometriuli kvlevis safuZvelze TagvebSi, romlebsac hqondaT

aloqsanuri diabeti dadginda pankreasis kunZulebSi β-ujredebis

odenobiTi simkvrivis Semcireba, maSin rodesac Aα da δD ujredebis

odenobiTi simkvrive momatebuli iyo.

Goke-s (27) gamokvlevებიT msubuqაd mimdinare eqsperimentuli

diabetis dros Aα da δD ujredebSi raime cvlilebebi ar aRiniSneba,

maSin rodesac diabetis mZime formis SemTxvevebSi β-ujredebi

ganicdian vakuolizacias, degranulacias, xoloAα da δD ujredebis

adgilmdebareoba Secvlilia periferiidan centrisaken.

Leiter et al. (26) ultrastruqturuli da imunohistoqimiuri kvlevis

safuZvelze, aloqsanuri diabetis dros TagvebSi eqsperimentis adreul

vadebze miuTiTeben β-ujredebis hipersekraciaze. maTi monacemebiTAα

daDδ ujredebi gadanacvlebulia kunZulis periferiidan centrisaken.

grZeli δD ujredebi penetrirebulia kunZulis siRrmeSi. mniSvnelovnad

gazrdilia Sexebis zedapiri Aα da δD ujredebs Soris. avtorebis (31)

mier eqsperimentSi radioimunuri da imunuhistoqimiuri kvlevis

meTodebis gamoyenebiT dadgenilia somatostatinis da glukagonis

raodenobis momateba sisxlSi, xolo insulinis koncentraciis Semcireba.

gazrdilia Aα da δ ujredebis raodenobac da zomebi, xolo β-ujredebis

Semcirebulia.

14

Tanamedrove morfologiis erT-erT centralur sakiTxs wamoadgens

qsovilTaSorisi urTierToba, kerZod parenqima-mikrocirkulaciuri

sistema-SemaerTebeli qsovili.

pankreasi aris maRali donis vaskuolirizaciis mqone organo,

romelsac aqvs SesaZlebloba awarmoos insulinis sekreti da

areguliros glukozis done sisxlSi (32, 33). gamokvlevebis safuZvelze

dadgenilia, rom Saqriani diabetis dros sxvadasxva organoebis wvril

sisxZarRvebSi, kerZod mikrocirkulaciur sistemaSi aRiniSneba

sisxlZarRvis kedlis hialinozi, plazmuri gaJRenTva, kedlis gasqeleba,

intimis gafaSreba da adgil-adgil endoTelis proliferacia.

morfologiuri cvlilebebis kompleqsi viTardeba mikrocirkulaciuri

sistemis, rogorc sisxlZarRvebSi, aseve perivaskularul zonaSi.

Aavtorebis (34-37) azriT pankreasis kunZulebi es is modelia,

romelzedac kargad Seiswavleba mikrovaskularuli kalapoti β-

ujredebTan erTad. rigiAmkvlevarebis (38, 39) mier aRwerilia pankreasis

kunZulebis kapilarebis morfologia da maTi roli kunZulebis

fiziologiuri funqciis ganviTarebaSi. Nnawilobriv Seswavlilia

pankreasis kunZulebis mikrocirkulaciis roli 1 tipis diabetis dros.

gamovlenilia pankreasis kunZulebSi sekretirebuli WEGF-A-s

(vaskulარuლ-endoTeluri zrdis faqtoris) moqmedeba endoTelis

gamtarobaze, ganxilulia mikrovaskularuli qselis ganviTareba da

funqcia janmrTel da daavadebul qsovilebSi. rigi avtorebis (33, 40)

monacemebiT insulindeficitur Tagvebis pankreasis kunZulebSi meti

kapilarebia, vidre janmrTeli Tagvebis pankreasis kunZulebSi,

Sesabamisad, kunZulebic ufro didia.

gansxvavebuli eqsperimentebis safuZvelze warmoiqmna azri (38, 40),

rom endoTeluri ujredebi ganapirobeben kunZulebis ganviTarebas.

bolo wlebis monacemebi pankreasis kunZulebis mikrocirkulaciur

სისტემაში mimdinare cvlilebebis paTo da morfogenezze Saqriani

diabetis dros sakmaod winaaRmdegobrivia. paTologebisaTvis da

klinicistebisaTvis sakmaod mniSvnelovania am cvlilebebis

morfogenezis kompleqsuri analizi. zemoTqmulidan gamomdinare, naTelia

Tu ra mniSvneloba aqvs im cvlilebebis Seswavlas, romlebic viTardeba

15

pankreasis kunZulebis mikrocirkulaciur სისტემაში Saqriani diabetis

dros.

Ptak-is (41) mier sinaTlis da eleqtronuli mikroskopiT Seswavlilia

Tagvebis pankreasis kunZulebi eqsperimentuli aloqsanuri diabetis

dros. maTi monacemebiT eqsperimentis sawyis vadebze aRiniSneba Zlieri

mononuklearuli infiltracia, rogorc pankreasis kunZulebSi, aseve

kunZulebis axlos. Espinoza et.al. (42) stresiT gamowveuli Saqriani diabetis

sawyis vadebze virTagvebis pankreasis kunZulebSi miuTiTeben

makrofagebis Zlier infiltraciaze. imunocitebi, romlebic avtorebis

mier identificirebuli iyo, rogorc makrofagebi imyofeboda

fagocitozis stadiaSi da inelebda daSlil β-ujredebs.

Vetere et al. (43) azriT Saqriani diabetis progresirebasTan erTad

makrofagebis raodenoba mcirdeba.

sakmaod sainteresoa imunokompetenturi ujredebis roli Saqriani

diabetis dros. cnobilia, rom I an iuveniluri tipis diabetis

SemTxvevaSi Timusidan miRebuli T-limfocitebi angreven kunZulebis β-

ujredebs.

NODDTagvebi (ara simsuqniT gamowveuli diabeti) xSirad gamoiyeneba

modelebad diabetis autoimunuri, anTebiTi formebis Sesaswavlad. Xu et

al. (44) aRniSnaven, rom I tipis diabetis dros endoTeluri ujredebis Sre,

romelic normalur pirobebSi warmoadgens bariers leikocitebisaTvis,

dazianebulia da saSualebas aZlevs T-limfocitebs Sevidnen kunZulebSi

da daazianon β-ujredebi.

amgvarad arsebuli literaturuli monacemebi morfologiur

cvlilebebze pankreasSi eqsperimentuli diabetis dros arc ise cotaa,

Tumca MmiRebuli Sedegebi sakmaod gansxvavebulia, rac rogorc Cans

ganpirobebulia eqsperimentis sxvadasxva vadebiT, romelic tardeba

gansxvavebul eqsperimentul cxovelebze. zemoTqmulidan gamomdinare

aSkaraa Tu ra mniSvneloba aqvs yvela am cvlilebebis Seswavlas da

sistematizacias.

Saqriani diabetis dros did Teoriul da praqtikul interess

warmoadgens kunZulovan qsovilSi mimdinare kompensatoruli da

16

regeneraciuli procesebis Seswavla, ramdenadac am procesebis

intensioba ganapirobebs insularuli ukmarisobis simZimes. struqturul

doneze insularuli ukmarisobis kompensacia xorcieldeba ZiriTadad 2

gziT: hormonoproduqciis gaZlierebiT darCenili ujredebis funqciuri

aqtivobis gazrdis xarjze, an insularuli ujredebis raodenobis

momatebiT (45-48).

β-ujredebis Senacvlebis Terapiis gamoyenebis სaWiroebam, rac

warmoadgens β-ujredebis transplantaciis (49) alternativas , gamoiwvia

kvleviTi samuSaoebis Catarebis აუცილებლობა β-ujredebis generaciis

sakiTxebze pankreasis (50-54) da ara pankreasis warmoSobis gansxvavebuli

ujredebidan (54-57).

kvlevebisa da axali hipoTezebis safuZvelze aRwerilia β-

ujredebis aRdgenis gansxvavebuli gzebi: arsebuli β-ujredebis

replikaciiT (50, 52, 58) da proliferaciiT (59-67), pankreasis sadinrebis

epiTelis neogeneziT da diferenciaciiT (68-79) pankreasis

diferencirebuli ujredebis (acinaruli, pankreasis sadinrebis

epiTeluri) transdiferenciaciiT (80-85), pankreasis zogierTi kunZulSida

arsebuli ujredebis neogeneziT da transdiferenciaciiT (86-89),

pankreasis gareT arsebuli ujredebis da Rerovani ujredebis

diferenciaciiT e.w. transdiferenciaciiT (6, 55-57, 70, 90-99). D

Liu et al. (94) azriT eqsperimentul TagvebSi β-ujredebis generacia

winamorbedi ujredebidan damokidebulia kunZulebis dazianebis xarisxze

da cxovelebis asakze. Tschen et al. (100) monacemebiT asakovan TagvebSi Bβ-

ujredebis generaciis unari Semcirebulia. De Tata et al. (101) aseve Tvlian,

rom es procesi Senelebulad mimdinareobs asakovan TagvebSi.

Waguri M. et.al. (102) Seiswavles ra ujredebSi mimdinare regeneraciuli

procesebi, daadgines, rom aloqsanis perfuziiT gamowveuli seleqciuri

dazianebis dros pankreasis kunZulebis segmentებSi aRiniSneba β-

ujredebis destruqcia, xolo araperfuzirebul segmentebSi β-ujredebi

SenarCunebulia. histologiuri suraTis mixedviT aloqsaniT

perfuzirebul segmentebSi gamovlenilia axlad warmoqmnili kunZulebi,

maSin rodesac araperfuzirebul segmentebSi aRiniSneba arsebuli β-

17

ujredebis proliferacia. eqsperimentis adreul vadebze kunZulebi,

rogorc zomiT ise raodenobrivad Semcirebulia, maSin roca mogvianebiT

matulobs kunZulebis mimdinare sivrce, izrdeba calkeuli β-ujredebis

zoma, romlebic axlo SexebaSia sadinris epiTelTan da rogorc Cans am

ujredebidan diferencirdebian. avtorebis azriT axali β-ujredebis

diferenciacia da proliferacia aris pankreasis kunZulebis

regeneraciis gamoxatuleba.

rigi mklevarebis (60, 61, 65) azriT pankreasis endokrinul nawils

gaaCnia proliferaciis maRali unari. jer kidev Д. Ф. Благовидов, Д. С.

Саркисов (103) erTeul SemTxvevebSi aRniSnaven insularuli qsovilis

mkveTrad gamoxatul hiperplazias da, rom pankreasis rezeqciis Semdeg

darCenili qsovili ZiriTadad warmodgenilia kunZulovani ujredebiT.

pankreasis kunZulovani qsovilis mniSvnelovan momatebas pankreasis

rezeqciis Semdeg cxovelebSi adastureben Semdegi avtorebi (104-106). maTi

monacemebiT kunZulebis zrda xdeba darCenil kunZulebSi ujredebis

hiperplaziis, proliferaciis da replikaciis Sedegad an egzokrinuli

ujredebis endokrinul ujredebad formirebis gamo.

cnobilia, rom pankreasis kunZulebis β-ujredebs axasiaTebs

SezRuduli mitozuri aqtivoba. rigi avtorebis (107, 108) azriT dabali

mitozuri aqtivoba kritikuli xdeba insulindamokidebul diabetian

TagvebSi, romlebsac mkveTrad aqvT gamoxatuli β-ujredebis destruqcia.

saintereso kvlevebia (97, 109) Catarebuli embrionuli Rerovani

ujredebis insulinis Semcvel β-ujredebad diferenciaciis dasadgenad.

bolo wlebis dakvirvebebma (88, 98, 110) gviCvenes, rom Rerovani ujredebis

diferenciacia funqciurad aqtiur β-ujredebamde mimdinareobs sakmaod

nela, Aalternativaa organos Rerovani ujredebis identifikacia,

eqspansia, diferenciacia an arsebuli β-ujredebis replikaciaBBBonner-Weir

et al. (83). winamorbedebi, romlebic gamoyofili iyo embrionidan

warmoadgendnen namdvil Rerovan ujredebs, maSin rodesac winamorbedebi

gamoyofili zrdasruli pankreasidan in-vivo warmoadgendnen mouwifebul,

dediferencirebul ujredebs (93, 98, 111-113).

18

De Haro-Hernandes R.et al. (114) monacemebiT Fgama transgenur TagvebSi

kunZulebis β-ujredebis regeneracia ori gansxvavebuli gziT

xorcieldeba: sadinrebis epiTeliuri ujredebidan an arsebuli β-

ujredebis funqciuri aqtivobis gaZlierebiT.

Gu D. et.al. (63, 115, 116) Tvlian, rom streptozotociniani diabetis

dros transgenur TagvebSi xdeba pankreasis sadinrebTan axlos

arsebuli erTeuli ujredebis regeneracia da neogenezi. maTive

monacemebiT tranzituli ujredebi Seicaven rogorc egzokrinul, aseve

endokrinul granulebs, romlebic xSirad Cndebian streptozotocinis

maRali dozis Seyvanis Semdeg. Aamgvarad, avtorebi Tvlian, rom axali β-

ujredebi warmoiqmneba kunZulebSi pankreasis sadinrebis epiTeluri

ujredebidan.

dResdReobiT warmodgenilia β-ujredebis neogenezis gziT miRebis

Semdegi meqanizmebi: pankreasis sadinrebis epiTeluri ujredebis

dakvirtvis Sedegad miRebuli ujredebis diferenciacia da Semdgom

hormonis warmoqmna (58, 72-74) da sadinrebTan axlos myofi ujredebis

proliferacia. sakmaod Zneli Sesafasebelia am ori meqanizmidan romeli

TamaSobs ufro mniSvnelovan rols aRdgeniT procesebSi, Tumca ki,

avtorebis (58, 72) umetesoba emxroba pirvels. amgvarad β-ujredebis

neogenezi pankreasis sadinrebis epiTelis dakvirtviT da Semdgomi

diferenciaciiT SedarebiT kargad aris Seswavlili da dokumentirebuli

(58, 78).

Collombat P.H., et al. (117, 118) mier transkripciuli faqtoris Pax4-s

kontrolis qveS miRebuli difteriis toqsinis gamoyenebis Semdeg,

sadinris epiTeluri ujredebi warmoqmnian rogorc acinarul, aseve

endokrinul ujredebs. aqedan 60%-Si xdeba β-ujredebis aRdgena

hiperglikemiis cvlilebebiT. elastazas toqsinis gamoyenebis Semdeg ki

aRiniSneba acinaruli ujredebis kvdoma, am SemTxvevaSi pankreasis

sadinrebis epiTeluri ujredebi dasabams aZleven acinaruli ujredebs.

Brun et al.-is (119) kvleviT diabetian TagvebSi transkripciuli faqtoriP

Pax4 aaqtiurebs β-ujredebis proliferacias.

19

pankreasis kunZulebis realur zrdas mRrnelebSi da adamianebSi

winamorbedebisagan Tavis kvlevebSi aRniSnaven Bonner-Weir et al. (113, 120).

maTi monacemebiT mRrnelebSi da virTagvebSi sadinrebis epiTelidan β-

ujredebis miReba mimdinareobs or talRad. 1. dabadebisTanave da 2. ZuZus

danebebis Semdeg. arsebobsHhipoTeza, rom postnatalur პერიოდში

kunZulebis ganviTarebis mTavar gzaს warmoadgens neogenezi da rom

pankreasis sadinrovan epiTeliums aqvs unari warmoqmnas axali kunZulebi

(75, 121).

rigi avtorebis azriT (122, 123) neogenezis procesis

gaaqtiurebisaTvis aucilebelია winamorbedi ujredebis stimulacia

sxvadasxva agentebiT; magaliTad zrdis faqtoriT (124), zrdis

epidermuli faqtoriT (67, 125), gastriniT (126, 127), glukagonis msgavsi

peptidebiT (128-130), aqtiviniT da betaceluliniT (131, 132), eqsidin-4-iT

(133, 134) da sxva faqtorebiT. zemoTCamoTvlili nivTierebebi calcalke

an kombinaciaSi astimulireben neogenezs. neogenezis Sesaxeb monacemebi

sakmaod gansxvavebulia da rogorc Cans ganpirobebulia Saqriani

diabetis gansxvavebuli eqsperimentuli modelebidan miRebuli SedegebiT,

romelSic monawileoben sxvadasxva cxovelebi Tagvebi, virTagvebi,

bocverebi da sxva. arsebuli Sromebi (53, 86, 128, 135) miuTiTeben

neogenezis arsebobaze, rogorc axalSobilebSi, aseve zrdasrul

organizmis pankreasSi kunZulebis dazianebis dros. M rigi avtorebi (106,

136) aseve aRweren Tagvebisa da virTagvebis pankreasis qsovilSi

mimdinare regeneraciul procesebs, sxvadasxva dazianebis SemTxvevebSi

da stimulaciis Semdeg. savaraudoa, rom sadinrovani ujredebis

populaciebi muSaoben, rogorc multipotenturi winamorbedebi romlebic

axdenen, rogorc egzokrinuli, aseve endokrinuli ujredebis generacias

(113, 137-139).

dResdReobiT β-ujredebis neogenezi warmodgenilia sadinrebis

dakvirtuli epiTeluri ujredebidan da aseve replikaciiT (50, 52, 58),

magram arc erTi ar warmoadgens eqskluzivs. axali β-ujredebis miReba

winamorbedebisagan garda am ori meqanizmisa SeiZleba moxdes

transdiferenciaciis gziTac (82, 140-143).A BB

20

Bonner-Weir et al.-is (58) monacemebze dayrdnobiT wamoyenebulia

hipoTeza, rom pankreasis sadinrebis diferencirebul epiTelur

ujredebs SeuZliaT funqcionireba dabadebis Semdeg, rogorc axali

kunZulebis winamorbedebs, momavalSi xdeba am ujredebis replikacia da

regresi ufro naklebad diferencirebul fenotipebSi da mxolod amis

Semdeg SeiZleba moxdes axali kunZulebis da acinusebis formireba.

aSkaraa, rom transdiferenciaciis dros, regresi da dediferenciacia

adreul vadebze normaluri procesia (111, 144).

epiTeluri ujredebis dediferenciacia xSirad asocirdeba epiTelur

mezenqimur gardaqmnasTan (99, 145, 146). Carlsson et al.-s (147) miaCnia, rom

epiTelur mezenqimuri gardaqmna warmoadgens erT-erT fiziologiur

safexurs pankreasis qsovilebis regeneraciis procesSi.

mniSvnelovania diskusia, kerZod sakiTxi acinozuri da kunZulovani

ujredebis urTierTgardaqmnis SesaZleblobaze, romelic daiwyo jer

kidev didi xnis win da dRemde grZeldeba (148). adre arsebuli

warmodgenis Tanaxmad acinozur da kunZulis ujredebs gaaCniaT

erTimeoreSi gadasvlis unari Tumca Semdgomma monacemebma mTlianad ar

daadastura am azris siswore. acino-insularuli transformacia,

rogorc paTologiis dros, ise fiziologiur mdgomareobaSi aRwerilia

rig kvlevebSi (81, 85, 115). acinozuri ujredebis gardaqmna kunZulovanSi

xdeba acino-insularuli fazis doneze, romlis drosac arsebobs

garkveuli mdgomareoba acinussa da kunZulebis inkretorul ujredebs

Soris (α, β da δ). eleqtronul-mikroskopuli kvlevis safuZvelze

ავტორები (149). aRniSnaven, rom acino-insularuli transformacia iwyeba

acinozuri ujredebis bazalur nawilSi, icvleba mitoqondriebi,

mcirdeba granularuli endoplazmuri badis odenoba, izrdeba

ribosomebis ricxvi, Cndeba kunZulebis ujredebisaTvis damaxasiaTebeli

specifikuri granulebi, romelTa raodenoba TandaTanobiT matulobs.

rigi avtorebis mier (71, 85, 143, 150, 151) insulindamokidebuli

diabetiT daavadebulebSi histologiuri, imunohistoqimiuri meTodebiT

gamovlenilia β-ujredebis struqturuli Tvisebebis mqone ujredebi

pankreasis acinusebSi. acinarul β-ujredebs axasiaTebdaT maRali

21

sekretoruli aqtiვoba da amasTan ar aRiniSnebodaT aSkarad gamoxatuli

destruqciuli cvlilebebi, ramac safuZveli misca mkvlevarebs

ganexilaT es ujredebi, rogorc funqciurad aqtiuri ujredebi. nawili

mkvlevarebisa (81, 115) Tvlis, rom acinaruli ujredebi endokrinuli

ujredebis niSanTvisebebiT gardamavali tipis ujredebia, romlebic

warmoiqmneba acinარულi ujredebis endokrinulSi transformaciis

Sedegad.

Яглов-is (152) hormonaluri profilis mixedviT arCevs sami tipis

acino-kunZulovan ujredebs (α, β da δ) ganasxvavebs egzokrinul da

endokrinul tips. К. А. Зуфаров da Tanaavtorebma (149) Seiswavles ra

pankreasis kunZulovani aparati sxvadasxva funqciur mdgomareobaSi

daadgines, rom virTagvebs, romlebsac xangrZlivi drois ganmavlobaSi

periodulad aZlevdnen glukozas didi doziT, ganuviTardaT didi

raodenobiT acinaruli ujredebi β-ujredebis niSan TvisebebiT, xolo

virTagvebს, romlebic SimSilobდნen, moemataT acinaruli ujredebis

raodenoba Aβ-ujredebis niSanTvisebebiT. am monacemebma safuZveli misca

avtorebs evaraudaT acinozuri ujredebis endokrinul ujredebad

transformaciis SesaZleblobaze, Tumca am azrs ewinaaRmdegeba Яглов В. В.

(152), is am ujredebs miiCnevs damoukidebel ujredebad, romlebsac

gaaCniaT Tavisi damaxasiaTebeli funqcia. Catarebuli kvlevis

safuZvelze Tvlis, rom acino-insularuli ujredebi, ara garadamavali

tipis ujredebia, aramed damoukidebeli ujredebi, romlebic

warmoadgenen insulinmaproducirebeli qsovilis evoluciis magaliTs.

eqskretoruli da kunZulovani qsovilis urTierTkavSirze miuTiTebs Д.

Ф. Благовидов-i da Д. С. Саркисов-ic (103). sadinrovani ligaciis

SemTxvevebSi adamianebis da virTagvebis pankreasSi acino-insularul

transdiferenciaciaze miuTiTeben Tavis SromebSi rigi avtorebisa (81).

Tumca ki am avtorebma (153, 154) verc erT seriuli anaTalze ver

daafiqsires sadinrebis epiTeluri ujredebis gadasvla uSualod

kunZulovan ujredebSi sadinrovari ligacis dros.

22

Minami et al. (151) aRniSnaven, rom cxovelebSi (TagvebSi da

virTagvebSi) insulinis warmomqmneli ujredebis generacia xdeba

acinaruli ujredebidan transdiferenciaciis gziT.

acinaruli ujredebidan β-ujredis warmoqmnaze arsebuli Sromebi

sakmaod gansxvavebulia. mTeli rigi avtorebis SromebSi (111, 153, 155)

aRwerilia acinarul kunZulovani transdiferenciacia daDam procesis

stimulirebis gzebi.BTumca ki rigi kvlevebis (154) Tanaxmad

eqsperimentSi acinaruli ujredebidan warmoiqmneba acinaruli da

sadinrovani ujredebi da ara β-ujredebi. rigi mklevarebis (105, 136) mier

nawilobrivi pankreatomiis dros aRiniSneba axali acinaruli ujredebis

warmoqmna. cxadia sakiTxi acino-insularuli transformaciis Sesaxeb

jer kidev moiTxovs Seswavlas. sadReisod regeneratoruli procesis

gamoxatulebad SeiZleba miviCnioT is axal warmonaqmnebi, romlebic

viTardebian wvrili gamomtani sadinrebis epiTelidan.

β-ujredebis erT-erT potenciur wyarod miiCneva TviT kunZulebSi

arsebuli ujredebi. fakultaturi ujredebis proliferaciiT da

rediferenciaciiT xdeba β-ujredebis warmoqmna kunZulebSi (61, 104, 119).

glukagonis warmomqmneli ujredebi aris pirveli endokrinuli

ujredebi, romlebic ganicdian diferenciacias da transformacias

insulin warmomqmnel ujredebad replikaciis gziT (86, 87, 89).

eqsperimentul kvlevebSi aRwerilia β-ujredebis regeneracia

kunZulSida α-ujredebidan. TagvebSi, romlebSiac β-ujredebi

dazianebuli iyo streptozotociniT da glukagonis warmomqneli α-

ujredebi gvevlineboda rogorc β-ujredis fenotipi. eqsperimentis

dawyebidan ramodenime Tvis Semdeg avtori (29) aRniSnavs sisxlSi

glukozis donis normalizacias. igive Sedegebi iqna miRebuli TagvebSi,

romelTa β-ujredebi dazianebuli iyo streptozotociniT. α-ujredebis β-

ujredebSi gardaqmnis SesaZleblobaze streptozotocian TagvebSi aseve

miuTiTeben sxva avtorebic (118). sainteresoa Sromebi, romlebSiac

aRniSnulia rom eqtopiuri eqspresia Pax4 iwvevs α-ujredebis

transdiferenciacias β-ujredebSi (Tagvebi). arsebuli kvlevebi

aradamajerebelia da moiTxovs Semdgom gagrZelebas, raTa gavigoT

23

warmoadgenen, Tu ara α-ujredebi β-ujredebis warmoqmnisaTvis

potenciur wyaros.

damtkicebulia, rom ganviTarebis embrionalur periodSi pankreasis

kunZulebis egzokrinuli da endokrinuli nawili viTardeba erTi

embrionuli Canasaxidan-endodermidan. es ki imis sasrgeblod laparakobs,

rom mas SenarCunebuli aqvs morfologiuri poliponetoba (112, 121, 135,

137, 156).

mTeli rigi kvlevebisa (56, 95, 157, 158), aseve eZRvneba β-ujredebis

generacias arapankreasuli warmoSobis ujredebidan. mniSvnelovani cda

iyo migveRo β-ujredebi, RviZlidan, Zvlis tvinidan da amnioturi

siTxidan in vitro magram zemoT CamoTvlili mcdelobebi iyo an

aradamajerebeli an negatiuri.

Aamgvarad β-ujredebis intensiuri diferenciacia da regeneracia

xels uwyobs β-ujredebis masis zrdas da Sesabamisad hormon insulinis

kompensacias (45, 52, 159) arsebuli Sromebi miuTiTeben, rom axali β-

ujredebi SeiZleba Seivsos pankreasis sadinrovani, wilSigniTa

sadinrebTan axlos arsebuli, centroacinaruli, acinaruli, kunZulSida

endokrinuli da Rerovani ujredebidan. dRemde Catarebuli kvlevebi

winaaRmdegobrivia da srulad ar asaxavs ujredebSi mimdinare

kompensatoruli procesebis morfologiur suraTs. rogorc Cans, β-

ujredebSi mimdinare kompensatoruli procesebis morfologiuri

kriteriumi arasakmarisad aris Seswavlili da moiTxovs kvlevebis

Semdgom gagrZelebas. K

klinikuri da eqsperimentuli kvlevebiT (10, 160, 161) dadgenilia

reproduqciuli hormonebis roli pankreasSi mimdinare adaptaciur

procesebSi Saqriani diabetis dros. cnobilia, Saqriani diabetis erT-

erT seriozul garTulebas warmoadgens reproduqciuli asakis

mamakacebSi sasqeso funqciis rRveva ganpirobebuli androgenebis

metabolizmis moSliT. cvlilebebi androgenebis metabolizmSi, Tavis

mxriv gavlenas axdens anabolizmis procesebze, romlebic regulirdeba

insulinis mier. literaturuli monacemebiT (162) androgen receptorebi

aqtiur monawileobas Rebuloben pankreasis kunZulebis ujredebSi

24

mimdinare adaptaciur-kompensaciur procesebSi da androgenuli

regulaciis efeqturoba ganisazRvreba, rogorc hormonis koncentraciiT,

aseve androgenuli receptorebis SemcvelobiT organoSi.

rigi avtorebis (161, 162) azriT eqsperimentuli diabetis dros androgen

receptorebi Tagvebis pankreasis kunZulebSi aregulireben ujreduli

procesebis farTo speqtrs, iseTebs rogoricaa proliferacia,

diferenciacia, apoptozi. zemoTqmulidan gamomdinare naTeli xdeba Cveni

interesi egzogenuri anrogenebis moqmedebisadmi metabolur da

kompensatorul procesebze Saqriani diabetis dros. D

amgvarad aSkaraa Tu ra mniSvneloba aqvs pankreasSi mimdinare yvela

cvlilebebis Seswavlas da sistematizacias eqsperimentuli diabetis

pirobebSi.

25

მასალა და მეთოდები

eqsperimentSi gamoyenebuli iyo 8 kviris asakis Wistar-is jiSis, orive

sqesis 120 virTagva, daaxloebiT 200 gr woniT. aqedan 90 virTagva iyo

samizne, 30 ki sakontrolo. 90 samizne virTagva daiyo 3 jgufad. 1

jgufSi iyo 30 virTagva erT Tviani aloqsanuri diabetiT,Mmeore jgufSi

30 virTagva erT Tviani aloqsanuri diabetiT, romlebsac ukeTdebodaT

plaferonis (0,25 mg/g) ineqciebi kunTebSi 10 dRis ganmavlobaSi da

meoTxe jgufi-30 mamri virTagva aloqsanuri diabetiT, romlebsac ori

kviris ganmavlobaSi ukeTdeboda 0,5 mg sinTezuri radioinertuli

androgen-meTiltrienoloni intraperitonealurad. diabets viwvevdiT

aloqsanis 150 mg 10% iani xsnaris erTjeradi SeyvaniT

intraperitonealurad. sakontrolo da samizne cxovelebi

gadanawilebuli da moTavsebuli iyvnen galiebSi. oTaxSi 12/12 sT-iT

(dRe-Rame), naTel-bneli cikliT, 22-25 C temperaturaze. aloqsanis

Seyvanis Semdeg 24 saaTis ganmavlobaSi cxovelebi ikvebebodnen

Tavisuflad da iRebdnen Saqrian wyals. mTeli eqsperimentis

ganmavlobaSi virTagvebi imyofebodnen kvebis srulfasovan, Sereul

racionze da wyals iRebdnen SeuzRudavi raodenobiT. aloqsanuri

diabetis simZime isazRvreboda glukozisa da imunoreaqtiuli insulinis

(IRI) SemcvelobiT sisxlSi. cxovelebSi glukozis koncentracia

plazmaSi maRal dones aRwevda 2 dReSi, xolo stabiluri diabeti

yalibdeboda 2 kviris manZilze. masalas viRebdiT eqsperimentis

dawyebidan 30, 40 da 44 dRis Semdeg. Eeqsperimentis bolos xdeboda

cxovelebis dakvla. cxovelebis eqsperimentidan gamoyvana warmoebda

intraperitonealurad 1 % etaminal-natriumis SeyvaniT.

26

ალოქსანი

aloqsani (2, 4, 5, 6-pyrimidinetetrone) aris glukozis toqsiuri analogi,

romelic amorCeviTad moqmedebs insulinis mwaromebel β-ujredebze,

azianebs am ujredebs da iwvevs adamianebSi arsebuli I tipis msgavs

Saqrian diabets eqsperimentSi. (163, 164).

პლაფერონი LB

plaferoni miRebuli iyo placentis amnioturi garsidan 1980 wels.

Aal. naTiSvilis sax. Eeqsperimentuli morfologis institutSi

mecnierTa jgufis mir akad. v. baxutaSvilis xemZRvanelobiT. Seswavlili

iyo plaferonis qimiuri, biologiuri da Terapiuli Taviseburebebi (165,

166). Catarebuli gamokvlevebiT dadginda, rom plaferoni (amnioturi

peptidi) aris biologiurad aqtiuri nivTiereba, romelic xasiaTeba

anTebis sawinaaRmdego, imunomamodulirebeli, antivirusuli,

antibaqteriuli, antiapoptozuri, hipoglikemiuri TvisebebiT. D

ჰისტოლოგიური კვლევა

histologiuri gamokvlevisaTvis masala fiqsirdebოდა 10 %

formalinSi, karnuasa da buenis safiqsacio narevSi. 5, 10 da 30 mk.

parafinis anaTlebis SeRebვa xdeboda hematoqsilin-eoziniT,

aldegidfuqsiniT, grimeliusiT, tolouidinis lurjiT da

pikrofuqsiniT van-gizonis mixedviT.

27

ელექტრონულ-მიკროსკოპული კვლევა

eleqtronul-mikroskopuli kvlevisaTvis pankreasis qsovilis wvrili

nawilebi 2 saaTis ganmavlobაში Tavsdeboda koloidur buferze (Ph 7,2 -

7,4) axlad momzadebul 2% osmiumis mJavis xsnarSi +4 C,

Ggauwylovanebisa da aRmaval koncentraciis spirtebSi gatarebis Semdeg

masala yalibdebოდა aralditis an epon 812-is narevSi. polimerizacias

vawarmoebdiT +58 C ocdaoTxi saaTis ganmavlobaSi.

ultraTxeli anaTlebi mzaddeboda LKB-III ultratomze. masalas

vRebavdiT uranilacetatiT reinoldcis mixedviT. ris Semdeg tardebოდა

gamokvleva eleqtronuli mikroskopiT „TeslaBS-500“ (gadideba 9000 - 22000),

dabeWdvisas negatiuri gamosaxuleba diddeboda 3-5-ჯერ.

ელექტროnul-მორფომეტრული კვლევა

eleqtronul suraTebze β-ujredebis da insulinis granulebis

raodenobis, procentuli Semadgenlobis, diametris da farTobis

gasazomad gamoviyeneT Adobe Photoshop CC. zomebis gadasayvanad

piqselebidan mikrometrebSi vxemZRvanelobdiT Semdegi formuliT (M X N

/10000) X K, M aris mikroskopis obieqtivis gadideba, gamosaxuli

piqselebSi, K aris TviTon suraTis resolution (piqseli/sm-ze), N TviTon

suraTis gadidebaa (suraTis sigrZe sm. gamravlebuli resolution-ze

rezoluciaze da gayofili monitorze gamosaxuli suraTis gadidebaze

anu 100 %, 10000 ki aris sm-Si mikrometrebis raodenoba. gamoTvlebiT

miviReT rom 41 piqseli tolia 11 µm-isa. Ddazomvebi vawarmoeT am

monacemebis mixedviT. monacemebis statistikuri damuSavebisaTvis

gamoviyeneT IBM SPSS Statistics 20.

28

იმუნოჰისტოქიმიური კვლევა

gamosakvlevi masalis fiqsacia warmoebda 10% formalinis buferul

xsnarSi (Ph 7,2-7,3) 10sT-is ganmavlobaSi, ris Semdegac qsovilis nimuSebs

vayalibebdiT parafinSi. imunohistoqimiuri kvlevisaTvis 3-4mk sisqis

anaTlebis deparafinizacia tardeboda standartuli wesiT. pirveladi

antisxeulebis saxiT gamoyenebuli iyo specifikuri antisxeulebi Mouse

Monoclonal CK19 (clone RCK108,1:50 dilutionDAKO), Mouse Monoclonal Endothelial Cell

Marker CD34 (clone QBEnd/10, dilution 1;100,DAKO),and guinea pig anti-swine insulin

antibody( dilution 1:100 DAKO,Carpinteria, CA,USA ), vizualizaciis sistemis

saxiT gamoyenebuli iyo sistemaAABC Staining System („DAB Novocastra“),

birTvebi damatebiTad iRebeboda harisis hematoqsilinis wyalxsnariT.

kontrolis saxiT viyenebdiT mwarmoeblis mier rekomendirebul

SeRebvas pirveladi antisxeulebis gareSe araspecifikuri reaqciis

gamoricxvis mizniT.

ელექტრონul-რადიოავტოგრაფული და რადიოიმუნური კვლევა

kortikosteronis (B),Bsomatotropinis (CTG), sasqeso steroidebis

(T,E2) gansazRvra warmoebda radioimunologiurad komerciuli (Kit)

krebulis gamoyenebiT.AvirTagvebis pankreasSi androgenebis

receptorebis (AR) gamosavlenad dakvlis win 1 saaTiT adre

intraperitonealurad Segvyvavda sinTezuri radioaqtiuri androgen-

meTiltrienoli (R-1881). dakvlis Semdeg masalis nawils vwonidiT da

homogenizaciis Semdeg vaTavsebdiT scintilaciur siTxeSi.

radiometruli kvlevisaTvis gamoyenebuli iyo aparati ”Бета”. masalis

meore nawili muSavdeboda radioavtografiis klasikuri meTodiT.

moniSnuli struqturebi-androgen receptorebi (AR) iTvleboda 900

gadidebaze. Ppankreasis biosinTezuri aqtivoba isazRvreboda dnm-is da

29

rnm-is sinTezis doniT. eleqtrono radioavtografuli kvlevisaTvis

qsovilis 1X0,5 mm zomis naWrebi Tavsdebოდა penicilinis boTlebSi 5 ml

are 199,1 % xbos SratSi. Semdeg Segvyavda dnm-isa da rnm-is radioaqtiurი

winamorbedები da tardebოდა inkubacia TermostatSi 380C temperaturaze

90 wT-is ganmavlobaSi. inkubacia warmoebდა gancalkevebulad dnm-is (20

mk.Ki/ml H3-TimidiniT fardobiTi aqtivoba 21.6 Ki/mM) da rnm-is (40

mk.Ki/ml. H3-uridiniT, fardobiTi aqtivoba 24 Ki/mM) radoaqtiuri

winamorbedebiT. inkubaciis dasrulebis Semdeg qsovilis naWrebs

vavlebdiT civ mkvebav areSi, homogenizaciis Semdeg vaTavsebdiT

scintilaciur siTxeSi. radioaqtivobis daTvla xdeboda aparat ‘‘Бета”-s

meSveobiT.

სტატისტიკური ანალიზი

monacemebis maCveneblebs Soris gansxvavebis sandoobis Sesamowmeblad

gamoyenebuli iqna stiudentis kriterumi T.

30

გამოკვლევის შედეგები

ვირთაგვების პანკრეასის მორფო-ფუნქციური თავისებურებანი ალოქსანური დიაბეტის

დროს

intravenurad aloqsanis diabetogenuri dozis Seyvanis Semdeg

virTagvebSi aRiniSneba glukozis mrudis cvlilebis ramodenime faza.

pirveli faza: hiperglikemiuri, romelic maqsimums aRwevda pirveli 2-4

saaTis ganmavlobaSi. zogierT virTagvaSi hiperglikemiuri faza

elviseburad gadadioda hiperglikemiurSi, zogjer ki hiperglikemiuri

sindromi yalibdeboda mxolod aloqsanis Seyvanidan 3-4 dRis Semdeg;

meore faza: hipoglikemiuri faza_zogjer mkveTrad iyo gamoxatuli da

ZiriTadad vlindeboda 14-24 saaTis ganmavlobaSi. hipoglikemiuri

sindromis Tavidan acilebis mizniT, cxovelebs winaswar eZleodaT

tkbili wyali. sacdel cxovelebs, romlebsac glukozis raodenoba

sisxlSi hqondaT 80 mg%-ze naklebi ukeTdebodaT 40 ml. glukozis

xsnariDda bolo mesame faza myari hiperglikemiuri faza. glukozis

mrudis es cvlilebebi yovelTvis ar viTardeboda kanonzomierad,

zogjer erT-erTi faza ar iyo mkveTrad gamoxatuli. aRsaniSnavia, rom

yvela virTagva erTnairad ar reagirebda aloqsanis Seyvanaze.

eqsperimentis dawyebidan 2 kviris Semdeg sacdeli cxovelebis sisxlSi

aRiniSneboda glukozis maRali maCveneblebi (250-320 mg% da zeviT).

SemdgomSi, zogierT cxovelSi es maCvenebeli ar icvleboda da rCeboda

igive, rac adრeul vadebze. zogierT cxovelebSi glukozis koncentracia

sisxlSi matulobda (500 mg% da zeviT), maSin rodesac mTel rig

cxovelebSi is mcirdeboda arsebul maCvenebelTan SedarebiT da ar

aRemateboda 170 mg/%. iyo aseve virTagvebi, romlebsac dasawyisSiac ki ar

aReniSnebodaT Zlieri hiperglikemia. msubuqi mimdinareobis aloqsanuri

diabetis dros pirveli Tvis ganmavlobaSi glukozis raodenoba sisxlSi

iyo 130-140 mg/%. saSualo simZimis dros 170-180 mg/%. mZime aloqsanuri

diabetis dros ki glukozis Semcveloba sisxlSi aRemateboda 250 mg/%.

31

სacdeli cxovelebi myari hiperglikemiiT kargavdnen wonas,

gamoxatuli iyo poliuria, polidifsia, polifagia. mZime mimdinareobis

aloqsanuri diabetis dros aRiniSnebოდა wonis mkveTri dakleba, Tmis

cvena, dispepsiuri movlenebi (zogjer sisxliani faRaraTi), umadoba,

mkveTrad gamoxatuli sisuste. ramodenime virTagvas mZimed mimdinare

aloqsanuri diabetis dros ganuviTardaT trofiuli wylulebi.

Catarebuli histologiuri gamokvlevebis safuZvelze dadginda, rom

aloqsanis Seyvanidan 1 Tvis Semdeg pankreasis kunZulebi Secvlilia

zogi kunZuli hipertrofulia, zogi atrofirebuli, nawili kunZulebisa

Seicavs nekrozul kerebs garSemortymuls SemaerTebelqsovilovani

kafsuliT (sur. 1). kunZulebSi aRiniSnebა uweso formis fibrozuli

CanarTebi. gansakuTrebiT dazianebulia didi kunZulebi, patara

kunZulebi naklebadaa Secvlili. mZimed mimdinare aloqsanuri diabetis

dros pankreasis kunZulebis dazianebis xarisxi Rrmavdeba. pankreasis

kunZulebis meti nawili atrofirebulia. zogierT kunZulebSi β-ujredebi

ganicdian Zlier destruqciul cvlilebebs degranulacias,

vakuolizacias. gvxvdeba didi raodenobiT danekrozebuli β-ujredebi

(sur. 2), gansakuTrebiT mZimed mimdinare diabetis dros (glukoza

sisxlSi 250 mg/%-ze meti) zog kunZulSi didi nekrozuli kerebi

SemosazRvruliა SemaerTebelqsovilovani kafsuliT, xolo zogi kunZuli

Cakirulia, kalcificirebuli. mkveTrad aris gamoxatuli wilTaSua da

kunZulebTan axlo mdebare acinusebs Soris fibrozi. kunZulebSi

kolagenuri boWkoebi sxvadasxva mimarTulebiT arian ganlagebuli da

kapilaris garSemo qmnian erTgvar “muftebs.” ujredebs Soris farTo

napralebSi Cazrdili boWkoebi uxeSia da xasiaTdeba maRali

fuqsinofiliiT. pankreasis kunZulebis struqtura Zlier darRveulia.

Eeleqtronul-mikroskopuli kvlevis safuZvelze eqsperimentis

dawyebidan 1 Tvis Semdeg pankreasis kunZulebSi mZimed mimdinare

eqsperimentuli diabetis dros aRiniSneba β-ujredebis aSkara

destruqciis niSnebi, gvxdeba didi nekrozuli kerebi da apoptozuri

ujredebi (sur. 3-4). nawili β-ujredebisa SeSupebulia, maT citoplazmaSi

alag-alag gvxvdeba ganaTebuli ubnebi, an didi zonebi amovsebuli

32

gamWirvale nivTierebebiT, Cndeba vakuolebi, birTvebi naTelia, qromatini

araTanabarzomieradaa gadanawilebuli. aloqsanis Seyvanidan 1 Tvis

Semdeg β-ujredebSi adgili aqvs qromatinis kondensacias birTvis

membranis maxloblad. birTvis membranis cvlilebebs Tan axlavs misi

konturis mkveTri Semcireba. birTvebi piknozuria da danawevrebuli.

mitoqondriebi Zlier Secvlilia, osmiofiluri, wvrili, aRiniSneba

kristebis dezorganizacia. marcvlovani endoplazmuri bade

fragmentirebulia, misi membrana vakuolizirebulia sxvadasxva xarisxiT.

vakuolebisagan Tavisufal adgilebSi ribosomebi jgufebadaa

ganlagebuli. didi raodenobiTaa umwifari granulebi da lizosomebi.

mwife sekretoruli granulebis raodenoba mcirea.

insulinmaproducirebuli ujredebi ganicdian Zlier degranulacias

(sur. 5). paralelurad zemoT aRwerili β-ujredebisa am vadaze

gamovlenilia sxva tipis β-ujredebic, romelTa raodenobac, rogorc

Cans damokidebulia paTologiuri procesis simZimeze. msubuqi

mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 130-140 mg/%)

dazianebul ujredebTan erTad gvxvdeba “naTeli” da “muqi” β-ujredebic.

umetesoba β-ujredebisa Tavisi erT-erTi polusiT uSualod exeba

kapilars. “naTel“ ujredebSi ujredSida organelebi da marcvlovani

endoplazmuri bade kargadaa ganviTarebuli da ukavia citoplazmis

mniSvnelovani nawili. marcvlovani endoplazmuri badis

cisternebisaTvis damaxasiaTebeli paraleluroba darRveulia,

cisternebis boloebi daxveulia. endoplazmuri badis membranebze

mimagrebulia ribosomebi. marcvlovani endoplazmuri badis boloebi

miqceulia goljis kompleqsisaken. β-ujredebSi goljis kompleqsi

kargadaa ganviTarebuli, misi struqturebi inarCuneben polarobas.

goljis kompleqsis “cis” boloze mravali buStukia, romlis membranebs

gaaCnia zeda nazi Sre. “trans” boloebze aRiniSneba mravalricxovani

sekretoruli granulebi, romlebic gamoirCeva dabali eleqtronuli

simkvriviT, maTSi Znelia naTeli arSiis garCeva, romelic gamoyofs

granulis SigTavss garsisagan. kapilaris diametri farToa kedeli

Txelia da gamofenilia endoTeliocitebiT, romelTa Soris

33

mravalricxovani fenestrebia, endoTeliocitebi Seicaven buStukebs.

kunZulis bazalur membranasa da kapilars Soris mWidro kontaqtia,

zogjer isini ise mWidrod arian erTmaneTTan dakavSirebuli, rom

bazaluri membrana Cans rogorc erTiani warmonaqmni. aseT ubnebSi

gamokveTili perikapilaruli sivrceebi ar vlindeba. zogierTi kunZulis

kapilarebs gorglis moyvaniloba aqvs. SemaerTebeli qsovilis raodenoba

mcirea da ar uSlis xels sekretis gadaadgilebas (sur. 6).

“muqi” tipis β-ujredebSi mitoqondriebi mcire raodenobiTaa, wvrili

zomis, uswormasworo, ganivad ganlagebuli kristebiT. mitoqondriis

matriqsi zomieri eleqtronuli simkvrivisaa. mitoqondriebi

koncentrirdebian goljis kompleqsTan. “muq“ ujredebSi sekretoruli

granulebi didi raodenobiTaa da avsebs mTel mis citoplazmas.

sekretorul granulebs sferuli moyvaniloba aqvT. mkveTradaa

gamoxatuli samfenovani membrana da eleqtronulad mkvrivi SigTavsi.

SigTavssa da membranas Soris rCeba naTeli zoli, romelsac araTanabari

sigane aqvs. Cans pinocitozuri an emiocitozuri buStukebi. xSirad erTi

sekretoruli granula ukavSirdeba meores da warmoiqmneba didi

buStukebi, ris Sedegad β-ujredebis citoplazmaSi Cndeba CaRmavebebi.

xSirad sekretoruli granulebis didi raodenoba uaxlovdeba

citoplazmur membranas da sekretoruli granulebis SigTavsi ujredSua

sivrceSi aRmoCndeba. zogierT adgilas Cans citoplazmuri badis grZeli

Sverilebi (sur. 7).

eqsperimentis 1 Tvis vadaze gvxvdeba aseve β-ujredebi, romlebSiac

mkveTrad aris gamoxatuli ujredSida organelebis momateba. adgili

aqvs intercisternuli granulebis formirebas marcvlovani

endoplazmuri badis RruebSi. marcvlovan endoplazmur badeze

mimagrebulia ribosomebi. intercisternuli granulebis SigTavsis

simkvrive SedarebiT mcirea mwife sekretoruli granulebis SigTavsis

simkvriveze. mwife granulebis raodenoba mcirea.

aloqsanis Seyvanidan 1 Tvis Semdeg pankreasSi kunZulebs gareT

gvxvdeba gardamavali tipis ujredebi. nawili am ujredebisa

moTavsebulia pankreasis sadinrebTan, nawili ki imyofeba acinusebTan

axlos, Tumca ki zRvari acinarul ujredebsa da am ujredebs Soris

34

mkveTrad aris SenarCunebuli (sur. 8). gardamavali tipis ujredebiს

umetesoba Seicavs pankreasis kunZulebis β-ujredebisaTvis

damaxasiaTebel erTeul dabali simkvrivis insulinis granulebs. aseT

ujredebs acinarul wilakSi gansxvavebuli lokalizacia aqvT. erT

wilakSi SeiZleba iyos 1-2 gardamavali tipis ujredი. am vadaze

virTagvebis pankreasSi aloqsanuri diabetis dros da sakontrolo

jgufebSi imunohistoqimiuri kvleviT, sadinrebis epiTelur ujredebis

citoplazmaSi aRiniSneba susti eqspresia CK 19-ze.

aloqsanis Seyvanidan 1 Tvis Semdeg cvlilebebi kapilarebSi ori

sxvadasxva xasiaTisaa: erTis mxriv Cans SeSupebuli endoTeluri

ujredebi, meore mxriv gamomSrali gauwylovnebuli endoTeliocitebi.

Aაseთ endoTelur ujredebSi organelebi gamomSralia, warmodgenilia

gawvrilebuli warmonaqmnebis saxiT. endoTelis plazma gafaSrebulia,

membranebi daSlili, zogjer adgili aqvs plazmolizs, ზოგ SemTxvevaSi

membranis naglejebi Cans kapilaris sanaTurSi (sur. 9). adgil-adgil

vlindeba endoTelis proliferacia. endoTelis citoplazmaSi

imunohistoqimiuri kvlevis Tanaxmad aRiniSneba susti eqspresia CD 34-ze

(sur. 10). eqsperimentis mZime mimdinareobis dros (glukoza sisxlSi 250

mg/%-ze meti), aloqsanis Seyvanidan 1 Tvis Semdeg kunZulis kapilaris

sanaTuri araTanabarzomieria, zog monakveTSi sisxlZarRvebi ara marto

gafarToebulia, aramed adgili aqvs sisxlis nakadis Senelebas, stazs.

zogierTi kapilari savsea formiani elementebiT. endoTeli gamomSralia,

gaTxelebuli, adgil-adgil kapilaris kedlis did monakveTSi aRiniSneba

endoTelis deformacia da misi gamozneqa kapilaris sanaTurSi. zogan

endoTeli Camofcqvnilia, fenestrirebuli, luminaruli zedapiri

gadasworebuliა, zogierT adgilas aRiniSneba wertilovani Caxevebi.

pinocitozi ar Cans (sur. 11). kapilaris sanaTurSi grovdeba daSlili

ujredebis, organelebis narCenebi. Eეleqtroნuli-radiavtografiiT zog

endoTelur ujredSi aღiniSneba H3–Timidinis CarTva. endoTeliocitebSi

H3–TimidiniT moniSvna Cans rogorc birTvSi, ise citoplazmaSi. erTeuli

endoTeliocitebi moiniSneba aseve H3–uridinze (sur. 12). am vadaze

adgili aqvs stromis SeSupebas, rac ganpirobebulia sisxlisZarRvebis

35

kedlis gamtarobis gazrdiT. zog perikapilarul sivrceSi gvxvdeba

amorfuli wvrilmarcvlovani masa da uxeSi kolagenuri boWkoebi,

romlebic mkveTrad osmiofiluria. yuradRebas ipyrobs kolagenuri

boWkoebi ganlagebuli kapilaris gaswvriv, romlebic Rrmad Sedian

kunZulSi, am adgilebSi kapilaris kedelSi vlindeba kaveolebi da

veziko-vakuolebi.

eqsperimentis dawyebidan 1 Tvis Semdeg aRiniSneba perikapilaruli

sivrcis da kunZulis Zlieri infiltracia makrofagebiT, plazmocitebiT,

fibroblastebiT (sur. 13). gvxvdeba erTeuli limfocitebic.

gansakuTrebiT yuradRebas iqcevs makrofagebi. makrofagebs aqvT sferuli

forma, birTvi ufro xSirad wargrZelebulia, zogjer mrgvali,

citoplazma marcvlovania. kargad aris ganviTarebuli marcvlovani

endoplazmuri bade. is ZiriTadad Sedgeba milakebisagan, romlebzedac

bevri ribosomaa. did momwifebul makrofagebSi marcvlovani

endoplazmuri bade gansakuTrebulad kargad aris ganviTarebuli, kargad

Cans goljis kompleqsic, romelic warmodgenilia brtyeli cisternebiT

da wvrili buStukebiT. aseT makrofagebSi zogjer Cans kontaqti

granularul da agranularul endoplazmur badeebs Soris.

citoplazmaSi sxvadasxva zomis da simkvrivis lizosomebia. makrofagebSi

vlindeba cximis wveTebi da daSlili ujredebis narCenebi. makrofagebs

gaaCniaT sxvadasxva zomis wanazardebi _ fsevdopodiebi. makrofagebi

moiniSneba rnm-is winamorbediT. makrofagebi H3-TimidiniT ar moiniSnebian

(sur. 14).

eqsperimentis erTi Tvis vadaze msubuqi mimdinareobis aloqsanuri

diabetis dros gansakuTrebiT bevria dabaldiferencirebuli da

axalgazrda fibroblastebi. momwifebuli fibroblastebi iSviaTad

gvxvdeba. dabaldiferencirebul fibroblastebs aqvT mrgvali birTvi da

SedarebiT martivi organizacia. proliferaciis adreul stadiaze

fibroblastebi saSualo zomisaa, aqvT varskvlaviseburi moyvaniloba.

maTSi marcvlovani endoplazmuri bade warmodgenilia mcire milakebiT

da cisternebiT, mravlad gvxvdeba ribosomebi da polisomebi,

mitoqondriebi gansxvavebuli zomisaa. dabaldiferencirebul

fibroblastebSi goljis kompleqsi sustad aris gamoxatuli.

36

marcvlovani endoplazmuri bade warmodgenilia milakovani cisternebiT,

romlebic ujredis sigrZivi RerZisakenaa orientirebuli. didi

raodenobiTaa Tavisufali ribosomebi. yuradRebas iqcevs vezikulebi da

pinocitozuri buStukebi. didi raodenobiTaa Tavisufali mitoqondriebi,

kristebis Cveulebrivi ganlagebiT. aseve vlindeba naTeli mitoqondriebi

mokle kristebiT. eleqtronul-radioavtografiuli meTodiT

dabaldiferencirebuli da axalgazrda fibroblastebi intensiurad

moiniSneba H3-TimidiniT, erTeuli fibroblastebi moiniSneba H3-uridinze.

mZimed mimdinare paTologiuri procesis dros gvxdeba sxvadasxva

simwifis fibroblastebi. dabaldiferencirebuli, axalgazrda

fibroblastebi cotaa. aRiniSneba mwife fibroblastebis didi raodenoba.

mwife kolagenmaproducirebel fibroblastebs kargad aqvT

ganviTarebuli endoplazmuri bade, is TiTqmis ikavebs mTel

citoplazmas da ujredi mogvagonebs Rrubels. goljis kompleqsi

nawilobriv reducirebulia. marcvlovani endoplazmuri badis

cisternebi xSirad erwymian citoplazmis membranas. eleqtრონul -

radiografiuli kvleviT fibroblastebi ar moiniSneba H3-Timidinze,

Tumca mkveTrad moiniSnebian H3-uridinze.

am vadaze didi raodenobiTaa plazmuri ujredebic eqscentrulad

ganlagebuli mrgvali an ovaluri birTviT, msxvili birTvakiT.

citoplazmaSi vlindeba mitoqondriebi, goljis kompleqsi, Cans

marcvlovani endoplazmuri badis niSnebi. arsebuli plazmuri ujredebi

არ moiniSneba Timidinis winamorbediT, Tumca sakmaod intensiuria

moniSvna H3-uridiniT.

eqsperimentis dawyebidan 1 Tvis Semdeg msubuqad mimdinare

aloqsanuri diabetis dros gvxvdeba mcire zomis limfocitebi.

limfocitebi osmiofiluria, rac ganapirobebs am populaciis muq fers.

birTvebi mrgvalia, birTvis membranaSi aRiniSneba invaginaciebi.

birTvakebi ar vlindeba, an moTavsebulia eqscentrulad da erwymis

birTvis heteroqromatinis grovebs. citoplazma osmiofiluria da

Sevsebulia mravalricxovani ribosomebiT. erTeul wvril mitoqondriebs

aqvT mkvrivi matriqsi. marcvlovani endoplazmuri badis cisternebi ar

Cans. eleqtrono-radioavtografiulma kvlevam gviCvena, rom patara

37

limfocitebis birTvebi moiniSneba H3-TimidiniT (sur. 15). aloqsanis

Seyvanidan 1 Tvis Semdeg, mZimed mimdinare paTologiuri procesisas

Cndeba saSualo da didi zomis limfocitebი. eleqtronul-

radioavtografiuli kvleviT saSualo da didi limfocitebi mkveTrad

moiniSneba H3-uridiniT. H3-uridini vlindeba birTvsa da citoplazmaSi.

vercxlis marcvlebi jgufebis saxiT ganlagebulia hetero da

euqromatinis sazRvarze. vercxlis marcvlebi citoplazmaSi metia,

vidre birTvze. gvxvdeba aseve muqi limfocitebi, romlebic

garSemortymuli arian naTeli qobiT. xSirad aseTi limfocitebi

imyofebian mWidro kontaqtSi endokrinul ujredebTan.

eqsperimentis dawyebidan 1 Tvis Semdeg α da δDujredebi

gadanacvlebulia kunZulis centrisaken (sur. 16). naxevrad Txel

anaTalze ujredebi dagrZelebulia. gazrdilia kontaqti α da

δDujredebs Soris. kerZod, msubuqi mimdinarebis aloqsanuri diabetis

dros (glukoza sisxlSi 170 mg/%) pankreasis kunZulebis α ujredebSi

sekretoruli granulebis raodenoba da SeRebvis intesioba didia, maSin

rodesac mZimed mimdinare aloqsanuri diabetis dros (glukoza sisxlSi

250 mg%) sekretoruli granulebis raodenoba Seucvlelia an

umniSvnelod matulobs. pankreasis kunZulebis α tipis ujredebi

ZiriTadad gvxvdeba kunZulis periferiul nawilSi, magram zogi maTgani

gadanacvlebulia centrisaken. Eeleqtroნul mikroskopuli kvleviT α

ujredebs aqvT ovaluri an poligonaluri forma. ujredebis citoplazma

dabali eleqtronuli simkvrivisaa, ujredSida organelebis simciris

gamo. marcvlovani endoplazmuri bade warmodgenilia mcirericxovani

cisternebiT, romlebzedac ribosomebi iSviaTadaa mimagrebuli.

citoplazmaSi gvxvdeba Tavisufali ribosomebi da poliribosomebi.

citoplazmis umniSvnelo nawili ukavia goljis kompleqs. goljis

kompleqsi warmodgenilia cisternebiT, mcire zomis vezikulebiT da

formirebadi sekretoruli granulebiT, romlebic dabali eleqtronuli

simkvrivisaa. mitoqondriebi cotaa, patara zomis, aqvT amodrekili

mTvarisebri forma, kristebis raodenoba mcirea da TviT mitoqondriebi

gabneulia mTel citoplazmaSi. sekretoruli granulebi sferuli

38

formisaa da dafarulia uwyveti samSriani membraniT. ujredebis SigTavsi

maRali eleqtronuli simkvrivisaa osmiofilobis gamo, bevria

hipergranulirebuli α ujredi. sekretoruli granulebi Tavisi

simravlis gamo avseben mTel citoplazmas. aseTi α ujredebis raodenoba

matulobs procesis simZimis proporciulad (glukoza sisxlSi 250 mg%-

ze meti).

eqsperimentis dawyebidan 1 Tvis Semdeg pankreasis kunZulebis δD

ujredebi uswormasworo an poligonaluri formisaa, zogi kunZulis

centrSia, zogi ki mcire raodenobiT periferiaze. momatebulia maTi

Sexebis zedapiri pankreasis kunZulebis α da β ujredebTan. eleqtroნul

-mikroskopuli kvlevis safuZvelze δDujredebis birTvi didia, masSi

qromatini Tanabrad aris gadanawilebuli. gvxvdeba ubnebi, sadac

sWarbobs euqromatini. marcvlovani endoplazmuri bade mcire

raodenobiTaa warmodgenili. organelebi xSirad polarulad aris

ganlagebuli. mravalricxovani sekretoruli granulebi moqceulia

sisxlaZarRvovani polusisaken. goljis kompleqsi kargad aris

ganviTarebuli da warmodgenilia mokle cisternebiT da

mravalricxovani vezikulebiT. goljis kompleqsis maxloblad xSirad

gvxvdeba formirebadi-sekretoruli granulebi. mitoqondriebi mcire

raodenobiT Seicavs wvril, momrgvalo-ovaluri, zogjer araswori

formis kristebs. iSviaTad gvxvdeba sekretoruli granulebi-mrgvali,

ovaluri formis, mkveTrad SemosazRvruli membraniT, romelic adgil-

adgil wyvetilia. membranis wyvetil adgilebSi granulebis SigTavsi

uSualo kontaqtSia hialoplazmasTan. δ ujredebis granulebis SigTavsis

simkvrive α da β ujredebis granulebis SigTavsis simkvriveze dabalia.

ujredebis granulebis simkvrive erTi da igive ujredSic ki SeiZleba

sxvadasxva iyos. granulebis SigTavssa da maT garss Soris sivrce

imdenad mcirea, rom eleqtronogramaze arc ki Cans.Ppankreasis

kunZulebis δ ujredebSi aloqsanuri diabetis msubuqi mimdinareobis

dros (glukoza sisxlSi 170 mg%-ze meti), granulebis raodenoba

umniSvnelod momatebulia, maSin rodesac aloqsanuri diabetis mZime

39

mimdinareobis dros (glukoza sisxlSi 250 mg/%-ze meti) mkveTrad

matulobs.

40

დანართი 1

suraTebi

sur. 1. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZulebi. zogi kunZuli atrofirebulia, zogi

hipertrofirebuli. nawili kunZulebisa Seicavs nekrozul kerebs,

garSemortymuls SemaerTebelqsovilovani kafsuliT.Hhematoqsilin

eozini X20.

41

sur. 2. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. aRiniSneba β-ujredebis nekrozi.

hematoqsilin eozini X40.

42

sur. 3. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. Ddidi nekrozuli kerebi. eleqtronuli

mikroskopia X9000.

43

sur. 4. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. didi raodenobiTaa apoptozuri

ujredebi. eleqtronuli mikroskopia X12000.

44

sur. 5. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. β-ujredSi mwife sekretoruli

granulebi. β-ujredebi ganicdian Zlier vakuolizacias, degranulacias.

eleqtronuli mikroskopia X10000.

45

sur. 6. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. zogierTi kunZulis kapilarebs

gorglis moyvaniloba aqvs. SemaerTebeli qsovilis raodenoba mcirea.

eleqtronuli mikroskopia X9000.

46

sur. 7. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. სekretoruli granulebis didi

raodenoba uaxlovdeba citoplazmur membranas. sekretoruli granulebis

SigTavsi ujredSua sivrceSia. zogierT adgilas Cans citoplazmuri

badis grZeli Sverilebi X6000.

47

სურ. 8. aloqsanuri diabeti virTagvas pankreasi. aloqsanis Seyvanidan 1

Tvis Semdeg. gardamavali tipis ujredebi. nawili am ujredebisa

moTavsebulia pankreasis sadinrebTan, nawili ki imyofeba acinusebTan

axlos, Tumca ki zRvari acinarul ujredebsa da am ujredebs Soris

mkveTrad aris SenarCunebuli. ეleqtroნuli-radiavtografiა. naxevarad

Txeli anaTali X1500.

48

sur. 9. aloqsanuri diabeti. virTagvas pankreasi. aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. sinusoidebis endoTelis plazmolema

gafaSrebulia, membranebi daSlili. adgili aqvs plazmolizs. zog

SemTxvevaSi membranis naglejebi Cans kapilaris sanaTurSi. eleqtronuli

mikroskopia X6000.

49

sur. 10. aloqsanuri diabeti. daavadebuli virTagvas pankreasi aloqsanis

Seyvanidan 1 Tvis Semdeg. pankreasSi aRiniSneba susti eqspresia CD-34-ze.

imunohistoqimia X40.

50

sur. 11. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. zogierTi kapilari savsea formiani

elementebiT. endoTeli Camofcqvnilia, fenestrirebuli, luminaruli

zedapiri gadasworebuliა, zogierT adgilas aRiniSneba wertilovani

Caxevebi. pinocitozi ar Cans. eleqtronuli mikroskopia X6000.

51

sur. 12. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. erTeuli endoTeliocitebi moiniSneba

H3–uridinze. eleqtronuli radioavtografia X6000.

52

sur. 13. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. aRiniSneba perikapilaruli sivrcis da

kunZulis Zlieri infiltracia makrofagebiT, plazmocitebiT,

fibroblastebiT. eleqtronuli mikroskopia X6000.

53

sur. 14. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan

1 Tvis Semdeg. pankreasis kunZuli. makrofagi mkveTrad moiniSneba H3-

uridinze. eleqtronuli radioavtografia X9000.

54

sur. 15. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. limfocitis birTvi moiniSneba H3-

TimidiniT. eleqtronuli radioavtografia X9000.

55

sur. 16. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1

Tvis Semdeg. pankreasis kunZuli. Aα da δD ujredebi gadanacvlebulia

kunZulis centrisaken. pankreasis kunZulis α ujredebSi sekretoruli

granulebis raodenoba didia. eleqtronuli mikroskopia X6000.

56

მორფოლოგიური ცვლილებები ვირთაგვების პანკრეასში

ალოქსანური დიაბეტის დროს და პლაფერონის ზემოქმედების

შემდეგ

aloqsanuri diabetis dawyebidan 1 Tvis da plaferonis 10 dRiani

kursis Semdeg aloqsan-plaferonis jgufis virTagvebSi glukozis

Semcveloba sisxlSi mcirdeba 50-60 mg% aloqsanur jgufTan SedarebiT,

Tumca ki metia sakontrolo jgufis virTagvebis glukozis donesTan.

glukozis donis cvlilebebi sisxlSi eqsperimentul da sakontrolo

jgufebSi damuSavebulia statistikurad da moyvanilia cxrilebSi (cxr.

1 da 2) (grafa 1).

aloqsan-plaferonis jgufSi virTagvebis wona aloqsanur jgufis

virTagvebis wonasTan SedarebiT Secvlili ar aris. pankreasis

kunZulebSi mniSvnelovani cvlilebebi ar aRiniSneba. Hhistologiurad

kunZulebi sxvadasxva zomisaa. zogi kunZuli hipertrofulia,

hiperemiulia, zogic atrofirebuli (sur. 17). rigi kunZulebis struqtura

darRveulia. pankreasis kunZulebis β-ujredebSi nekrobiozuli

cvlilebebis paralelurad gvxdeba erTeuli ujredebi, romlebSic

aRiniSneba mitozebi. vizualurad apoptozuri ujredebis raodenoba

Semcirebulia. aloqsan-plaferonis jgufis virTagvebis pankreasis

kunZulebSi kapilarebis endoTeli Txelia, kargad fenestrirebuli.

pankreasis kunZulebSi gvxvdeba bevri axlad warmoqmnili kapilari (sur.

18). imunohistoqimiuri kvlevis safuZvelze aloqsan-plaferonis jgufis

virTagvebis pankreasSi aRiniSneba CDD34-is Zlieri eqspresia kunZulebis

kapilarebis endoTelis citoplazmaSi (sur. 19). CD 34-is mimarT

imunoreaqtiuloba kunZulebSi da sadinrebis momijnave ujredebSi

maRalia. aloqsan-plaferonis jgufis virTagvebis pankreasSi CD 34-is

Semcveli pozitiuri ujredebi gabneulia mTel pankreasSi (sur. 20), maSin

rodesac aloqsanis da sakontrolo jgufis virTagvebis pankreasSi CD

34-is eqspresia sakmaod SezRudulia (sur. 21).

57

aloqsan-plaferonis jgufis virTagvebis pankreasSi perikapilaruli

sivrce gaganierebulia. fibrozuli CanarTebi mcire raodenobiTaa,

kolagenuri boWkoebi Txelia. perikapilarul sivrceSi da momijnave

qsovilebSi aRiniSneba makrofagebis, lifocitebis, plazmocitebis da

erTeuli fibroblastebis infiltracia. gansakuTrebul interess iwvevs

makrofagebi, eqscentrulad ganlagebuli didi birTviT. citoplazmaSi

kargad Cans ribosomebi, vakuolebi, fagocitebi, polisomebi da

lizosomebi. granularuli endoplazmuri bade Txelia da warmodgenilia

cisternebiT da vakuolebiT, romlebic axlos arian birTvTan.

makrofagebSi mitoqondriebi didi raodenobiTaa. makrofagebi intesiurad

moiniSnebian H3-Timidinze da H

3-uridinze (sur. 22).

aloqsan-plaferonis jgufis virTagvebis pankreasSi gansakuTrebul

yuradRebas ipyrobs gardamavali tipis β-ujredebis niSan Tvisebebis

Semcveli erTmaneTisagan gansxvavebuli ujredebi (sur. 23). am

gardamavali tipis ujredebs pankreasSi aqvT sxvadasxva lokalizacia.

nawili am ujredebisa moTavsebulia acinusebTan axlos, Tumca ki

sazRvari acinarul ujredebsa da gardamavali tipis ujredebs Soris

mkveTrad aris SenarCunebuli. nawili ujredebisa gvxdeba wilSida,

interlobulur da intralobulur sadinrebTan. wilSida sadinrebTan

arsebuli gardamavali tipis ujredebis apikaluri polusi aRwevs

sadinris sanaTurs, ujredis ZiriTadi masa ki moTavsebulia acinusis

bazalur nawilTan. აloqsan-plaferonis jgufis virTagvebis pankreasSi

gardamavali tipis ujredebi imyofebian diferenciaciis da simwifis

sxvadasxva xarisxSi da mdgomareobaSi. imunohistoqimiuri kvlevis

safuZvelze CK 19-is eqspresia aRiniSneba pankreasSi arsebul sadinrebis

epiTelur ujredebis citoplazmaSi (sur. 24). anti CK 19-ze iRebeba

wvrili, interlobuluri da intralobuluri sadinrebis ujredebi. CK

19-is eqspresia ZiriTadad vlindeba pankreasis kunZulebTan axlos myofi

sadirebis epiTeluri ujredebis citoplazmaSi. gansakuTrebiT Zlieri

eqspresiaa ujredis bazalur nawilSi. CK 19-is susti eqspresia vlindeba

acinarul ujredebSi da TiTqmis ar aris kunZulebis ujredebSi.

insulinis granulebis SeRebvis intensioba cvalebadia da ZiriTadad

58

ufro mkveTria kunZulebis axlos arsebul sadinris epiTelur

ujredebSi. eleqtronogramaze zog ujredSi insulinis granulebis

raodenoba mcirea, zogierT ujredebSi ki bevri da Sesabamisad

aRiniSneba cvalebadi intesiobis SeRebva anti insulinze (sur. 25).

eleqtronogramaze zogi gardamavali tipis ujredi Seicavs

acinarul da β-ujredisaTvis damaxasiaTebel niSnebs (sur. 26). aseTi

gardamavali tipis ujredebis erTi polusi miqceulia kunZulisaken და

Seicavs β-ujredebisaTvis damaxasiaTebel granulebს mkveTrad

gamoxatuli garsiT, kerZoT mkvrivi guliT da asimetriuli naTeli

arSiiT. citoplazmis es monakveTi dabali eleqtronuli simkvrivisaa,

vinaidan is Tavisufalia organelebisagan. marcvlovani endoplazmuri

badis cisternebs ara aqvT egzokrinuli ujredebisaTvis damaxasiaTebeli

paraleluroba da warmodgenilia vezikulebiT. mokle cisternebi

erTmaneTSia gadaxlarTuli, ribosomebi mcire raodenobiTaa. zogierT

ujredSi marcvlovani endoplazmuri bade vlindeba CanarTis saxiT,

swored am ubnebSi didi raodenobiTaa β-insulocitebis granulebi,

mitoqondriebi wvrilia, Seicavs erTeul kristebs da naTel matriqs, rac

aseve damaxasiaTebelia β-ujredebisaTvis. citoplazmis sxva ubnebSi

SenarCunebulia marcvlovani endoplazmuri badis cisternebis

paraleluroba, amave dros mitoqondriebi msxvili, momrgvalo-ovaluri

formisaa, gaaCnia eleqtronulad mkvrivi matriqsi da mravalricxovani

kristebi, aqve vlindeba zimogenuri granulebi e.i. yvelaferi is rac

damaxasiaTebelia egzokrinuli ujredebisaTvis (sur. 27).

ეleqtronogramaze nawili ujredebisa moTavsebulia acinusებTan axlos

da Seicavs pankreasis kunZulebis β-ujredebisaTvis damaxasiaTebel

granulebs, romlebic imyofebian perinuklearul zonaSi an kidev

ujredis erT erT polusTan. am ujredebis birTvs gardamavali

(Sualeduri) agebuleba aqvs, kerZod qromatinis masaSi sWarbobs

euqromatini. imunohistoqimiuri kvlevis safuZvelze aloqsan-plaferonis

jgufis virTagvebis pankreasis erTeuli acinaruli ujredebi iRebeba

anti insulinze. insulinis granulebis SeRebvis intesioba cvalebadia da

ZiriTadad ufro mkveTria kunZulebis axlos.

59

eleqtronogramaze pankreasis kunZulebSi Zalian iSviaTad gvxvdeba

gardamavali tipis ujredebi, romelic erTdroulad Seicaven

α-ujredebisaTvis damaxasiaTebel glukagonis da β-ujredebisaTvis

damaxasiaTebel erTeul insulinis granulebs (sur. 28).

60

დანართი 2

suraTebi

sur. 17. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. pankreasis kunZulebi. zogi kunZuli hipertrofulia,

hiperemiulia, zogic atrofirebuli. hematoqsilin eozini X40.

61

sur. 18. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. pankreasis kunZulebSi gvxvdeba bevri axlad

warmoqmnili kapilari. eleqtronuli mikroskopia X6000.

62

sur. 19. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. kunZulebis kapilarebis endoTelis citoplazmaSi

aRiniSneba CDD34-is Zlieri eqspresia. imunohistoqimia X40.

63

sur. 20. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. CD 34-is Semcveli pozitiuri ujredebi gabneulia

mTel pankreasSi. imunohistoqimia X40.

64

sur. 21. aloqsanisa da sakontrolo jgufis virTagvebis pankreasi. CD 34-

is eqspresia sakmaod SezRudulia. imunohistoqimia X40.

65

sur. 22. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. makrofagi intesiurad moiniSneba H3-Timidinze da H

3-

uridinze. eleqtronuli radioavtografia X14000.

66

sur. 23. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. gardamavali tipis ujredebi. nawili ujredebisa

gvxdeba wilSida, interlobulur da intralobulur

sadinrebTan.Eeleqtronuli radioavtografia. naxevrad Txeli anaTali

X1500.

67

sur. 24. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. CK 19-is Zlieri eqspresia pankreasis kunZulebTan

axlos myof sadinrebis epiTelur ujredebis citoplazmaSi.

imunohistoqimia X40.

68

sur. 25. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. pankreasis kunZulebTan axlos myofi sadirebis

epiTelur ujredebSi aRiniSneba cvalebadi intesiobis SeRebva anti

insulinze. imunohistoqimia X40.

69

sur. 26. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. Aacino-insularuli ujredi. Uujredi Seicavs β-

ujredebisaTvis damaxasiaTebel insulinis maproducirebel, aseve

acinaruli ujredebisaTvis damaxasiaTebel zimogenur granulebs.

eleqtronuli mikroskopia X9000.

70

sur. 26. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. acino-insularuli ujredi. ujredi Seicavs β-

ujredebisaTvis damaxasiaTebel insulinis maproducirebel granulebs,

citoplazmis sxva ubanSi SenarCunebulia marcvlovani endoplazmuri

badis paraleluroba. eleqtronuli mikroskopia X12000.

71

sur. 28. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).

virTagvas pankreasi. gardamavali tipis ujredi erTdroulad Seicavs α-

ujredebisaTvis damaxasiaTebel glukagonis da β-ujredebisaTvis

damaxasiaTebel erTeul insulinis granulebs. eleqtronuli mikroskopia

X6000.

72

cxrili 1. glukozis da insulinis Semcveloba virTagvebis sisxlSi aloqsanuri diabetis dros, plaferonis

Syvanamde da plaferonis Seyvanis Semdeg.

ჯგუფი საშუალო

მაჩვენებელი

სტანდარტული

გადახრა

კორელაციის

კოეფიციენტი r

სტიუდენტის

კრიტერიუმი t

სანდოობა

p

glukoza პლაფერონის

შეყვანამდე

211.57 12.18 r =0.732 p=0.000

18.160

0.000

glukoza პლაფერონის შეყვანის

შემდეგ

172.29 6.16

საკონტროლო ჯგუფი 80.86 8.51

insulin plaferonis Seyvanamde

5.81 0.24

insulini plaferonis Seyvanis Semdeg

9.16 0.22

sakontrilo jgufi 25.46 0.34

gansxvaveba statistikuradDsandoa (t=18.160; p=0.000)

plaferonis Seyvanis Semdeg standartuli gadaxris mniSvneloba sakmaod dabalia, rac efeqtis erTgvarovnebaze

metyvelebs. korelaciis koeficientis dadebiTi mniSvneloba miuTiTebs imaze, rom yvela SemTxvevaSi aRiniSneba

dadebiTi efeqti. saSualo maCveneblebs Soris gansxvavebis sandoobis Sesamowmeblad gamoyenebul iqna stiudentis

kriteriumi t. amasTanave, sakontrolo jgufebis Sedarebisas stiudentis kriteriumi iyo ori damoukidebeli

SerCevisaTvis.

73

cxrili 2. საშუალო მაჩვენებლების (N=10) განაწილება დღეების მიხედვით.

grafa 1. insulinis Semcveloba sisxlSi.

74

ალოქსან-პლაფერონის ჯგუფის ვირთაგვების პანკრეასში

კუნძულ გარეთ არსებული იზოლირებული β-უჯრედები და

მათი ფუნქციური მდგომარეობის შეფასება ელექტრონულ-

მორფომეტრული მეთოდით

zogierTi kunZulgareT arsebuli β-ujredebi izolirebulia da ar

aris organizebuli kunZulebSi. sazRvari am ujredebsa da acinusebs

Soris mkveTrad aris gamoyofili. es ujredebi Seicavs β-ujredebisaTvis

damaxasiaTebel insulinis granulebs. Aam tipis β-ujredebSi kargad

vlindeba, rogorc naTeli, aseve muqi insulinis granulebi. muqi

insulinis granulebi warmodgenilia mkvrivi guliT da garSemo TeTri

haloTi, maSin rodesac naTel granulebs gaaCniaT eleqtrono naTeli

guli da TeTri halo. insulinis granulebis umetesoba moTavsebulia

perinuklearul zonaSi (sur. 29). Aam β-ujredebis birTvi didia da masSi

sWarbobs euqromatini. Cvens mier eqstra insularul komponentaT

miCneuli iyo is izolirebuli ujredebi, romlebSiac kargad vlindeboda

birTvi da mwife insulinis granulebi. swored am ujredebis funqciuri

mdgomareobis gansasazRvrad vawarmoeT β-ujredebSi insulinis

granulebis raodenobis, diametris, farTis, naTeli da muqi granulebis

procentuli Sesabamobis gansazRvra da Sedareba aloqsanuri da

sakontrolo jgufis virTagvebis pankreasis kunZulebis β-ujredebis

Sesabamis parametrebTan erTi da igive zomis fragmentebSi. miRebuli

monacemebis safuZvelze dadginda rom aloqsan-plaferonis jgufis

virTagvebis pankreasis izolirebul β-ujredebSi insulinis granulebis

raodenoba naklebia, vidre aloqsanis da sakontrolo jgufis

virTagvebis pankreasis kunZulebis β-ujredebSi. aloqsan-plaferonis

jgufSi naTeli insulinis granulebis procentuli raodenoba metia,

xolo muqis naklebia aloqsanur da sakontrolo jgufTan SedarebiT.

samive jgufis β-ujredebSi sxvaoba insulinis granulebis diametrSi ar

75

aRiniSneba. miRebuli monacemebi damuSavebulia statistikurad da

moyvanilia cxrilSi (cxrili 3).

76

დანართი 3

suraTebi

sur. 29. aloqsanuri diabeti da plaferoni. kunZul gareT arsebuli

izolirebuli β-ujredi.insulinis granulebis umetesoba moTavsebulia

perinuklearul zonaSi. eleqtronuli mikroskopia X9000.

77

cxrili 3. insulinis granulebi virTagvebis pankreasSi aloqsan-plaferonis jgufis izolirebul β-ujredebSi da

aloqsanur da sakontrolo jgufis pankreasis kunZulebis β-ujredebSi.

gansxvaveba statistikuradDsandoa *(p<0.0001)

ჯგუფი ფართობი ინსულინის

გრანულების

რაოდენობა

მუქი

ინსულინის

გრანულების

რაოდენობა

ნათელი

ინსულინის

გრანულების

რაოდენობა

მუქი

ინსულინის

გრანულების

პროცენტული

რაოდენობა

ნათელი

ინსულინის

გრანულების

პროცენტული

რაოდენობა

მუქი

ინსულინის

გრანულების

დამეტრი (µm)

მუქი

ინსულების

გრანულების

არეა (µm2 )

ნათელი

ინსულინის

გრანულების

დიამეტრი (µm)

ნათელი

ინსულინის

გრანულების

არეა (µm2)

I -

ალოქსან/პლაფერონის

ჯგუფი კუნძულ გარეთ

არსებული

იზოლირებული β-

უჯრედი

42.74

±

0.57*

113.75

±

9.55*

39.38

±

5.05*

74.38

±

5.09*

33.92

±

1.90*

66.07

±

1.90*

0.404

±

0.007*

0.143

±

0.009*

0.447

±

0.01*

0.165

±

0.007*

II –ალოქსანური

დიაბეტი ვირთაგვების

პანკრეასის

კუნძულების β-

უჯრედები

42.65

±

0.61*

136.41

±

4.74*

95.00

±

3.86*

41.00

±

2.51*

69.86

±

1.55*

30.14

±

1.55*

0.304

±

0.006*

0.076

±

0.03*

0.334

±

0.007*

0.095

±

0.04*

III - საკონტროლო

ჯგუფი ვირთაგვების

პანკრეასის

კუნძულების β-

უჯრედები

42.45

±

0.48*

344

±

0.51*

276

±

0.35*

68

±

0.71*

80.22

±

1.25*

19.78

±

1.25*

0.391

±

0.63*

0.06

±

0.05

0.397

±

0.68*

0.124

±

0.008

78

ჰორმონალურ-მეტაბოლური ცვლილებები მამრ ვირთაგვებში

ალოქსანური დიაბეტის დროს და სინთეზური რადიოინერტული

ანდროგენ მეთილტრიენოლონoს ზემოქმედების შემდეგ

meoTxe jgufis mamri virTagvebis sisxlSi aloqsanuri diabetis dros

eqsperimentis dawyebidan me-14 da 30-e dRes aRiniSneba glukozis

koncentraciis mniSvnelovani mateba, insulinis Semcvelobis kleba,

adaptaciuri hormonebis kortikosteronis (44%) da somatotropinis (38%)

mkveTri zrda, aromatizaciis procesebis aqtivacia, testosteronis

raodenobis Semcireba (52%) pankreasis β-ujredebSi dnm-isa da rnm-is (dnm-is

56%-iT, rnm-is58%-iT) sinTezis mkveTri kleba normasTan SedarebiT.

aloqsanuri diabetis dros, eqsperimentis dawyebdan 30-e dRes da or

kviriani siTezuri radioinertuli androgen-meTiltrieნolonis kursis

Semdeg virTagvebis sisxlSi glukozis koncentracia mcirdeba 23%-iT

sawyis maCvenebelTan SedarebiT. aRiniSneba kortikosteronis (27%) da

somatotropinis (75%) Semcvelobis Semcireba, aromatizaciis procesebis

aqtivaciis kleba, estradiolis da testosteronis plazmuri koncentraciis

mateba da miaxloeba normasTan (Tanafardobis koeficienti 0,008, norma

0,005). Tavisufali receptorebis Semcvelobis Semcireba 121% mde. maSin

roca sakontrolo maCvenedeli utoldeba 210%-s. dnm-isa da rnm-is sinTezis

mateba (dnm-is 16%-iT, xolo rnm-is 12%-iT). testosteronis miaxloeba

normasTan (92%) xels uwyobs androgenuli receptorebis aqtivacias,rasac

mosdevs organos mdgomareobis gaumjobeseba. pankreasis zogi kunZuli

hipertrofirebulia. aRiniSneba β-ujredebis proliferacia (sur. 30). zogi

β-ujredi aqtiurad moiniSneba dnm-iT (cxrili 4).

79

დანართი 4

cxrili 4. glukozis, insulinis (IR), testosteronis (T), estradiolis (E), kortikosteronis (K), somatotropinis (ST),

Semcveloba mamr virTagvebis sisxlSi, dnm da rnm siTezis aqtivobis cvlilebebi da androgen receptorebi pankreasis

β-ujredebSi aloqsanuri diabetis dros da siTezuri androgen meTiltrieნolonis zemoqmedebis Semdeg.

jgufebi Ddakvirvebis dReebi Gglukoza mg% IR

mkU/mg

T

ng/ml E2

ng/ml

Е2/Т ng/ml

В ng/ml

ST

ng/ml

DNA

mk.Ki/ml

RNA

mk.Ki/ml

AR

mk.Ki/ml

AR

‰

I

14

205

±

0,54*

12,74

±

0,46*

1,74

±

0,10*

0,018

±

0,002**

0,010

18,72

±

1,26*

1,26

±

0,01**

79116,9

±

12,42*

153948,5

±

22,15*

502,1

±

2,48*

19,91

±

2,01*

30

220

±

0,26*

4,82

±

0,24*

1,38

±

0,09*

0,023

±

0,003**

0,016

21,84

±

1,61*

1,98

±

0,06**

97483,3

±

24,11*

193762,8

±

15,08*

808,13

±

3,12*

33,32

±

1,64*

45

saboloo

180

±

0,84*

4,72

±

0,24**

2,41

±

0,09*

0,019

±

0,003**

0,008

20,15

±

0,90*

1,35

±

0,03**

113024,2

±

21,05*

207034,2

±

20,11*

476,9

±

1,92*

32,01

±

2,01* kontroli

125

±

0,16*

23,84

±

0,53*

2,61

±

0,23*

0,014

±

0,003*

0,005

13,00

±

1,30*

0,91

±

0,02*

141280,2

±

16,12*

265428,5

±

15,41*

394,2

±

1,42*

16,11

±

1,15*

*p=0.001 **p=0.01

80

sur. 30. virTagvაs pankreasis kunZuli. aloqsanuri diabetis dros da

sinTezuri radioinertuli androgen-meTiltrieნolonis zemoqmedebis

Semdeg ( ექსპერიმენტის 44 დღე). ჰემატოქსილინ ეოზინი X40.

81

გამოკვლევის შედეგების ანალიზი

Catarebuli kvlevis safuZvelze dadginda, rom virTagvebis pankreasis

kunZulebSi dazianebuli β-ujredebi an kapilaris garSemoa Tavmoyrili an

difuzuradaa gadanawilebuli sxva endokrinul ujredebs Soris.

sxvadasxva kunZulebSi am ujredebis raodenoba cvalebadia. gvxvdeba aseve

pankreasis kunZulebi nekrozis ubnebiT. aseTi ubnebi SemosazRvrulia

SemaerTebeli qsovilis kafsuliT. msubuqi mimdinareobis aloqsanuri

diabetis dros (glukoza sisxlSi 130-140 mg/%) eqsperimentis dawyebidan 1

Tvis Semdeg virTagvebis pankreasis kunZulebSi aRiniSneba β-ujredebis

destruqciuli cvlilebebi: degranulacia, vakuolizacia, iSviaTad

nekrozis niSnebi. amave dros aRsaniSnavia, rom ziandeba ufro didi zomis

kunZulebi, maSin rodesac patara zomis kunZulebi naklebadaa

dazianebuli. mZime mimdinareobis aloqsanuri diabetis dros (glukoza

sisxlSi 250 mg/% da meti) eqsperimentis dawyebidan 1 Tvis Semdeg

virTagvebis pankreasis kunZulovan qsovilSi β-ujredebSi insulinis

granulebi vlindeba sustad, an TiTqmis ar vlindeba, rac mowmobs am

ujredebSi insulinis totalur ukmarisobaze, e.i. maT srul gamofitvaze,

es aseve dasturdeba histologiuri, eleqtronul-mikroskopuli,

imunohistoqimiuri kvlevebiT sxva mkvlevarebis (4, 9, 11, 12, 14, 15, 17, 167-169)

mier.

ultrastruqturulma analizma saSualeba mogvca ufro TvalsaCinod

dagvedgina β-ujredebis dazianebis xarisxi da lokalizacia. Mmsubuqi

mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 130-140mg/%) β-

ujredebi warmodgenilia ZiriTadad “naTeli” da “muqi” β -ujredebiT.

“naTel” β-ujredebSi granulebis raodenoba cotaa. gansxvavebuli zomis da

simkvrivisE granulebi gafantulia mTel citoplazmaSi, an

koncentrirebulia ujredis erT-erT polusTan. aseT β-ujredebSi

organelebi SedarebiT mcire raodenobiTaa. “muqi” β-ujredebi didi

raodenobiT Seicaven sxvadasxva zomis granulebs, romlebic

Tanabarzomieradaa gadanawilebuli mTel citoplazmaSi da iRebebian

82

gansxvavebuli intensivobiT. “muq” β-ujredebSi organelebi aseve cotaa,

mcire zomis mitoqondriebSi gvxvdeba msxvili an ramodenime kompaqturad

ganlagebuli lipiduri CanarTebi. aris ujredebis gardamavali tipic,

saSualo zomis da simkvrivis insulinis Semcveli granulebiT, romlebic

Tanabradaa gadanawilebuli mTel citoplazmaSi. amgvarad, am sami qvetipis

β-ujredebs Soris pankreasis kunZulebSi gvxvdeba aseve β-ujredebi

destruqciis aSkara niSnebiT: citoplazmis vakuolizaciiT zogierT

kunZulSi aseTi ujredebi didi raodenobiTaa.

saSualo simZimis aloqsanuri diabetis dros (glukoza sisxlSi 170-180

mg%) eleqtronul-mikroskopuli kvlevis safuZvelze β-ujredebi ganicdian

TvalsaCino destruqciul cvlilebebs, xSirad aRiniSneba citoplazmis

degranulacia, sxvadasxva xarisxiT gamoxatuli vakuolizacia. zogierT

kunZulebSi gvxdeba nekrozuli ubnebi da daSlili β-ujredebi.

kapilarebis kedeli nawilobriv gasqelebulia, perikapilaruli sivrce

gazrdilia. perikapilarul sivrceSi Cans uxeSi kolagenuri boWkoebi,

romlebic gars exvevian kapilarebs da maT garSemo qmnian “muftebs”. rac

rasakvirvelia xels uSlis sekretis gadaadgilebas.

mZime mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 250

mg/%- ze meti), rogorc naxevrad Txel anaTlebze, ise eleqtronul-

mikroskopulad virTagvebis pankreasis kunZulebSi ZiriTadad Cans

danekrozebuli da apoptozuri β-ujredebi. amasTan erTad SenarCunebulia

erTeuli β-ujredebi destruqciis niSnebiT.

cnobilia, rom pirveli tipis diabeti xasiaTdeba pankreasis β-

ujredebis mniSvnelovani deficitiT, rac gamowveulia β-ujredebis

nekroziT da apoptoziT (7, 17, 170, 171). aloqsani gamoiyeneba specialurad β-

ujredebis dazianebisaTvis da iwvevs cxovelebSi I tipis diabetis msgavs

diabets. aloqsani azianebs β-ujredebis dnm-s da intracelularul

struqturebs, swored es aris nekrozis da apoptozis mizezi. β-ujredebSi

gazrdili apoptogenuri aqtivoba, rogorc Cans gamowveulia

mitoqondriuli membranis dazianebiT, romlis mizezs warmoadgens

intracelularuli kalciumis homeostazis moSla da mitoqondriuli

apoptozuri gzebis aqtivacia Smirnov et al. (171).

83

Catarebuli kvlevis safuZvelze unda iTqvas, rom danekrozebuli,

dazianebuli ujredebis raodenoba matulobs paTologiuri procesis

simZimis Sesatyvisad. kerZod, rac ufro mZimedaa gamoxatuli aloqsanuri

diabeti, miT ufro metia pankreasis kunZulebSi mesame jgufis ujredebi e.i.

miT ufro Rrmad arian β-ujredebi dazianebuli. amgvarad aSkaraa, rom

ZiriTad moments, romelic ganapirobebs daavadebis manifestacias, misi

mimdinareოbis simZimes aris pankreasis kunZulebis β-ujredebis dazianebis

xarisxi.

Catarebuli eqsperimentis safuZvelze pankreasis kunZulovan aparatSi

mimdinare cvlilebebis mixedviT mizanSewonilad CavTvaleT gamogveyo

Semdegi jgufebi:

I_pankreasis kunZulebSi β-ujredebi ar aris dazianebuli, an naklebad

dazianebulia;

II_pankreasis kunZulebSi mkveTrad aris gamoxatuli β-ujredebSi

destruqciis niSnebi, vlindeba ubnebi nekrozuli ujredebiT.

III_pankreasis kunZulebSi β-ujredebis umetesi nawili danekrozebulia,

vizualurad didi raodenobiT aris apoptozuri ujredebi. es cvlilebebi

da maSasadame dajgufebac pirdapir asaxavs paTologiuri procesis

simZimes.

cnobilia, rom pankreasis kunZulebSi β-ujredebi uSualo kontaqtSi

imyofebian pankreasis α da δ ujredebTan, romlebic Tavis mxriv

aproducireben hormonebs glukagons da somatostatins. aloqsanuri

diabetis sxvadasxva simZimis dros, am samive saxis ujredebis

urTierTdamokidebuleba sakmaod rTulia da moiTxovs Semdgom Seswavlas

kompleqsSi (23, 24, 26, 27, 172).

aloqsanuri diabetis dros paralelurad β-ujredebis dazianebisa,

aRiniSneba cvlilebebi pankreasis αAda δDujredebSiac. αAda δDujredebi

gadanacvlebulia centrisaken. Ggazrdilia β-ujredebis Sexebis zedapiri A

αAda δDujredebTan. ultrastruqturul doneze da SeRebviT glukagonis

granulebis Semcveloba pankreasis kunZulebis α-ujredebSi vizualurad

matulobs rogorc msubuqi, ise mZime mimdinareobis aloqsanuri diabetis

dros. mZimed mimdinare paTologiuri procesisas glukagonis granulebis

raodenoba da SeRebvis intensioba SedarebiT mcirea. amgvarad, granulebis

84

raodenobis momateba α-ujredebSi, rogorc Cans damokidebulia an

dakavSirebulia insulinis raodenobazec da mTlianad paTologiuri

procesis simZimeze. kerZod, arsebobs uSualo kavSiri insulinis

raodenobasa da glukagonis warmoqmnas Soris. cnobilia, rom glukagoni

ara marto Zlieri glikemiuri faqtoria, aramed is axdens mastimulirebel

zemoqmedebas β-ujredebis sekreciazeც (26-28), rac Tavis mxriv warmoadgens

erT-erT kompensatorul meqanizmს Saqriani diabetis dros. ar aris

gamoricxuli, rom glukagonis sekreciis gaZliereba SeiZleba iyos

dakavSirebuli insulinis kontregulaciuri funqciis amovardnasTan,

ramdenadac insulini mniSvnelovan rols TamaSobs α-ujredebis adeqvaturi

moqmedebis SenarCunebaSi W. Ham and D. Cormack (173).

aloqsanuri diabetis dros eleqtronul-mikroskopuli kvleviT

somatostatinis Semcveli granulebis raodenoba da SeRebvis intensioba δ-

ujredebSi gazrdilia. Tumca ki am momatebas gaaCnia specifikuri xasiaTi,

romelic ZiriTadad damokidebulia paTologiuri procesis simZimeze.

aloqsanuri diabetis msubuqi mimdinareobis dros somatostatinis

granulebis raodenoba δ-ujredebSi TiTqmis ucvlelia, maSin rodesac

mZimed mimdinare aloqsanuri diabetis dros vizualurad somatostatinis

granulebis raodenoba mniSvnelovnadaa momatebuli. cnobilia, rom

somatostatini amcirebs insulinis da glukagonis sekreacias, aqveiTebs

glukozis Sewovas nawlavebSi. Catarebuli eqsperimentebidan Cans

somatostatini TamaSobs mniSvnelovan rols mkveTrad gamoxatuli

glukagonis sekreciis pirobebSi, hiperglikemiis SezRudvis TvalsazrisiT.

somatostatinis es moqmedeba SeiZleba aixsnas, rogorc adgilobrivi

hormonis zemoqmedeba. rac Seexeba mis moqmedebas, rogorc namdvili

hormonisa, unda gaTvaliswinebuli iyos is faqti, rom somatostatini

warmoiqmneba ara marto δ-ujredebSi, aramed hipoTalamusis

periventrikularul da arkualur birTvebSic. somatostatinis aqtivacia

iwvevs somatotropuli hormonis daTrgunvas, rac arapirdapiri

diabetogenuri faqtoria W. Ham and D. Cormack (173). amgvarad, Sesabamisi

hormonis momateba an Semcireba kunZulis ujredebSi miuTiTebs misi

biosinTezis gaZlierebaze an Semcirebaze. eqsperimentuli diabetis dros

rigi mkvlevarebi (26, 31, 174) radioimunuri meTodis safuZvelze aRniSnaven

85

insulinis raodenobis koncentraciis Semcirebas, xolo somatostatinis

da glukagonis koncentraciis momatebas sisxlis plazmaSi.

Catarebuli eqsperimentis safuZvelze gamovlinda urTierToba erTis

mxriv insulinis Semqmnel β-ujredebsa da Sesabamisad glukagonis da

somatostatinis Semcvel αAda δ ujredebs Soris. miRebuli Sedegebis

safuZvelze SeiZleba davaskvnaT, rom pankresis kunZulebis endokrinuli

ujredebis (β, α, δ) sapasuxo reaqcia eqsperimentul diabetis pirobebSi

damokidebulia daavadebis simZimeze da rom pankreasis kunZulebis

endokrinuli nawili naxSirwylebis cvlis moSlaze pasuxobs

kompleqsurad yvela misi komponentis metnaklebi monawileobiT.

pankreasi aris rTuli maRali donis vaskuolirizaciis mqone organo.

pankreasis kunZulebs da acinarul qsovils aqvT saerTo embrionuli

warmoSoba. pankreasis arteria amaragebs rogorc pankreasis kunZulebs,

aseve acinarul qsovils. kunZulebis vaskuolirizacia xasiaTdeba Semdegi

TvisebiT: kunZulebi iReben met sisxls, vidre acinusebi; kunZulebis

sisxlZarRvebs gaaCniaT meti xveulebi da meti simkvrive; kunZulebis

kapilarebi Seqmnilia fenestrirebuli endoTeluri ujredebiT; kunZulebis

kargad ganviTarebuli vaskuლარuლi sistema ganapirobebs maT Zlier

oqsigenacias acinarul qsovilTan SedarebiT (33, 38-40).

gansxvavebuli eqsperimentebis safuZvelze warmoiqmna azri, rom

endoTeluri ujredebi ganapirobeben kunZulebis ganviTarebas (32, 37).

arsebobs kunZulebis ganviTarebis orsafexuriani modeli. pirveli

safexuri-endoTeluri ujredebi ganapirobeben pankreasis kunZulebis

ganviTarebas sadinrebis epiTelidan, Sedegad kunZulis ujredebi

ukavSirdebian sisxlZarRvebs. meore safexurze axali endoTeluri

ujredebi anviTareben kapilarul bades kunZuls gareT. es ori modeli

xsnis, Tu rogor arian dakavSirebuli Bβ-ujredebi sisxlZarღvovan

sistemasTan Tavis ganviTarebis adreul da Semdgom periodSi. swored am

ori sistemis urTierTkavSiriT xdeba pankreasis kunZulebis sekretoruli

funqciis uzrunvelyofa (33, 35, 36).

amgvarad pankreasis mikrovaskularuli qseli kargi modelia imis

gasagebad, Tu rogor xdeba endoTeluri ujredebis monawileoba organo

specifiur anTebiT procesebSi. bolo wlebis monacemebi pankreasis

86

mikrocirkulaciur wreSi mimdinare cvlilebebis PpaTo da morfogenezze

Saqriani diabetis dros sakmaod qaoturi da winaaRmdegobrivia.

zemoTqmulidan gamomdinare paTologebisaTvis da klinicistebisaTvis

sakmaod mniSvnelovania am cvlilebebis morfogenezis kompleqsuri

analizi da sistematizacia.

eqsperimentis dawyebidan 1 Tvis Semdeg, msubuqi mimdinareobis

aloqsanuri diabetis dros, umetesi kapilarebis sanaTuri gafarToebulia,

kapilaris kedeli warmodgenilia mxolod endoTeliT, romelic Seicavs

mravalricxovan fenestrebs. endoTeluri ujredebi qmnian kapilarebs

kunZulebs SigniT, raTa β-ujredebis mier gamoyofil sekrets SeeZlos

moxvedra sanaTurSi. zog adgilas endoTeli ganicdis distrofias da

deskvamacias. pankrasis kunZulebSi β-ujredebi uaxlovdeba 1 an 2

fenestრirebul kapilars. swored fenestrebi aris is Cqari gza, romliTac

insulini Sedis sisxlZarRvis sanaTurSi. SemaerTebeli qsovilis

raodenoba mcirea da xels ar uSlis sekretis gadaadgilebas. sxvanairad

gamoiyureba kapilaruli qselis venuri monakveTi. kerZod, is kapilarebi,

sadac ZiriTadad mimdinareobs nivTierebaTa cvla. es kapilarebi

amofenilia endoTeliocitebis Txeli SriT, romelTa Soris vlindeba

mravalricxovani fenestrebi. fenestrebs gaaCniaT damaxasiaTebeli

safarveli-diafragma (romelic xuravs fenestrebs). swored kapilarebis es

monakveTi xasiaTdeba maRali ganvladobiT, vinadian gaaCnia gansakuTrebuli

napraliseburi sivrceebi-kontaqtebi endoTeliocitebs Soris. aseTi

napralisebri kontaqtebis arsebobaze miuTiTeben sxva avtorebic Зуфаров,

(149).

paTologiuri procesis progresirebasTan erTad sxvadasva monakveTSi

gvxdeba araTanabarzomieri kapilarebi, sakmaod msxvili endoTeluri SriT.

kargad Cans endoTeliocitebis birTvebi. sainteresoa, rom am monakveTSi

cotaa endoTeliocitebs Soris fenestrebi aseT monakveTebSi kapilarebis

endoTelSi gazrdilia vakuolebis, vezikulebis, kaveolebis raodenoba.

amgvarad kaveolebi, veziko-vakuolebi, rogorc Cans is gzebia, romelic

xels uwyobs insulinis transendoTelur gadaadgilebas aloqsanuri

diabetis dros da warmoadgens adaptaciur kompensatoruli procesis

gamoxatulebas. erTeul endoTelur ujredebSi gvxvdeba cximis wveTebi.

87

sisxlZarRvebis kedeli mniSvnelovani metaboluri unaris mqone organoa,

romelsac aqvs unari iseTi komponentebis warmoqmnisa da sinTezirebisa,

rogoricaa kolageni, elastini, glikozaminglikanebi da amave dros

monawileoba miiRos plazmis sxvadasxva komponentebis katabolizmSi,

pirvel rigSi lipidebis, e.i. im nivTierebebis, romlebsac gaaCniaT unari

gaiaron ujredul barierSi da Semdeg SeaRwion intimaSi. eqserimentis

adreul vadebze sisxlZarRvis kedelSi lipidebis moxvedra SeiZleba iyos

araregulirebadi endocitozis Sedegad, an kidev endoTeliocitebs Soris

sivrcis gazrdis gamo. mogvianebiT ki ukve lipidebis transporti xdeba

dazianebuli, daSlili endoTeliocitebis kerebSi.

mZimed mimdinare aloqsanuri diabetis dros (glukoza sisxlSi 250

mg/%) perikapilaruli sivrce gazrdilia. arteriolebi warmodgenilia

erTis mxriv SeSupebuli endoTeluri ujredebiT, meores mxriv gamomSrali,

gauwylovanebeli endoTeliocitebiT. aseT ujredebSi organelebs gaaCniaT

gamomSrali, wvrili warmonaqmnebis Sexeduleba: endoTelis plazmolema

gafaSrebulia, membranebi ganSrevebuli. zogjer aRiniSneba plazmolizic.

xSir SemTxvevaSi membranis naglejebi moCans kapilaris sanaTurSic.

zogierTi kapilaris sanaTuri Sevsebulia TrombocitebiT da

eriTrocitebiT, rogorc Cans endoTelis dazianebas mohyveba

eriTrocitebis zedapiris Secvla (eriTrocitebi glikozirebuli

hemoglobiniT da Secvlili zedapiriT), maTi aglutinacia, stazi da

bolos Trombocitebis adgezia. zog monakveTebSi endoTeli ganicdis

proliferacias. gvxdeba axlad warmoqmnili sisxlZarRvebi. eleqtronul-

radioavtografiuli kvleviT aseT adgilebSi endoTeluri ujredebi

moiniSneba H3-Timidinze. imunohistoqimiuri kvleviT kunZulebis

kapilarebis endoTelis citoplazmaSi aRiniSneba CD 34-is eqspresia.

zogierTi avtorebis monacemebiT (36) insulinis deficiti aZlierebs

vaskularul endoTeluri zrdis faqtoris (WEGF-A) sekrecias da xels

uwyobs axali sisxlZarRvebis warmoqmnas. rigi avtorebis (36, 38, 175) azriT

insulin deficitur TagvebSi kapilarebi kunZulebSi metia da kunZulebic

didia. amgvaradACven vTliT, iq sadac insulinis deficitia WEGF-A-s

gamoyofa gaZlierebulia, es ki Tavis mxriv xels uwyobs axali kapilarebis

warmoqmnas. rogorc Cans WEGF-A faqtoris zrdis sapasuxod xdeba

88

endoTelis proliferaciis gaZliereba, endoTelis migracia da axali

sisxlZarRvebis warmoqmna pankreasis kunZulebSi, rac dasturdeba

imunohistoqimiuri da eleqtronul-radioavtografiuli kvleviT. amgvarad

endoTeluri ujredebi warmoqmnian axal kapilarebs kunZulis SigniT rac

aseve warmoadgens kompensatorul adaptaciuri procesis gamoxatulebas.

aloqsanuri diabetis dros morfologiuri cvlilebebis kompleqsi

viTardeba pankreasis kunZulebis mikrocirkulaციური wris yvela rgolSi,

ziandeba arteriolebi, kapilarebi, venulebi, sisxlZarRvTSorisi

anastomozebi. Cveni monacemebiT pirvel rigSi ziandeba arteriolebi.

paTologiuri cvlilebebi viTardeba wvrili sisxlZarRvebis yvela

struqturebSi, aRiniSneba sisxlZarRvis kedlis hialinozi, plazmuri

gaJRenTva, kedlis gasqeleba, intimis gafaSreba da adgil-adgil

endoTelis proliferacia, kunZulebis gazrda axladwarmoqmnili

kapilarebis xarjze.

amgvarad pankreasis kunZulebis endoTeluri ujredebi TamaSoben

mniSvnelovan rols I tipis diabetis dros. endoTeluri Sre warmoadgens

mniSvnelovan bariers sisxlis ujredebisaTvis. β-ujredebi da

mikrovaskularuli sistema erTad, kooperirebulad monawileoben

glukozis homeostazSi (33, 40).

aloqsanuri diabetis dros alteraciul cvlilebebs kunZulebis

endoTelSi (distrofia, deskvamacia), mosdevs anTebiTi da imunuri

ujredebis migracia transendoTelur sivrceSi da qsovilebSi, β-ujredebis

Semdgomi dazianebiT. paTologiuri procesis progresirebasTan erTad

aRiniSneba stromis SeSupeba, rac rogorc Cans ganpirobebulia

sisxlZarRvis kedlis gamtarobis gazrdiT. perikapilarul sivrceSi

vlindeba amorfuli wvrilmarcvlovani masa da mkveTrad osmiofiluri

erTeuli uxeSi kolagenuri boWkoebi. kapilarebis gaswvriv ganlagebuli

kolagenuri boWkoebi Rrmad Sedian kunZulebSi. perikapilarul sivrceSi

da kunZulebSi aRiniSneba infiltracia fibroblastebiT, limfocitebiT,

maკrofagebiT da plazmocitebiT. deendoTilizaciis zonaSi xSirad Cans

limfocitebis adhezia. endoTelis dazianebis adgilebSi limfocitebi

gvxvdeba monocitebTan da granulocitebTan erTad. zogjer qafisebri

ujredebis grZeli morCebi nawilobriv gars exvevian limfocitebs.

89

Eleqtronulი-radioavtografiiT bevri limfocitis birTvi moiniSneba H3-H

Timidinze, rac miuTiTebs am ujredebis proliferaciuli aqtivobis

zrdaze, amazeve miuTiTeben rigi avtorebi (35, 39, 149). mZimed mimdinare

paTologiuri procesis dros pankreasis kunZulebSi endokrinul ujredebs

Soris gamovlenili limfocitebi awveba da azianebs endokrinul

ujredebs. aseT limfocitebs gaaCniaT organelebiT Raribi citoplazma,

marcvlovani endopllazmuri badis StrixebiT da mitoqondriebis

umniSvnelo raodenoba.

eqsperimentis dawyebidan 1 Tvis Semdeg gansakuTrebiT bevria saSualo

zomis, varskvlaviseburi moyvanilobis fibroblastebi. eleqtronul-

radioavtografiuli meTodiT kvlevisas msubuqad mimdinare

eqsperimentuli diabetis dros fibroblastebi intensiurad moiniSneba H3-

-TimidiniT, zogierTi ki H3-uridiniT. mZimed mimdinare paTologiuri

procesis dros fibroblastebis citoplazma aqtiurad moiniSneba H3-

uridiniT rac miuTiTebs kolagenis intensiur produqciaze.

aloqsanis Seyvanidan 1 Tvis Semdeg aRniSneba Zlieri mononuklearuli

infiltracia, rogorc pankreasis kunZulebSi, ise maT garSemo. imunocitebi,

romlebic identificirebulia makrofagebad vlindeba pankreasis

kunZulebSi. makrofagebis didi nawili imyofeba fagocitozis stadiaSi da

inelebs daSlil β-ujredebs da lipidebs. Mmakrofagebis mniSvnelovan

rolze dazianebul kunZulebSi miuTiTeben mklevarebi (41). makrofagebis

citoplazmaSi aRiniSneba sxvadsxva zomis da simkvrivis lizosomebis

arseboba. am adgilebSi zogjer Cans kontaqti granularuli da

agranularuli endoplazmis badeebs Soris. makrofagebs gaaCniaT

sxvadasxva zomis wanazardebi, fsevdopoidebi. Eleqtroნul-

radioavtografiuli kvleviT makrofagebi aqtiurad moiniSneba rnm-is

winamorbediT. makrofagebi sisxlZarvis kedlis erT-erTi ZiriTadi

Semadgeneli nawilia, romlebic STanTqaven ra lipidebs,

transformirdebian qafisebr ujredebSi. rigi avtorebisa did yuradRebas

uTmobs monocitarul warmoSobis makrofagebs, vinaidan maT didi

raodenobiT gaaCniaT lipid-receptorebi anu “skvenjer” receptorebi

dabali simkvrivis lipidebis (LDL da VLDL) STanTqvisaTvis. receptorebiT

ganapirobebuli lipidebis StanTqვa mimarTulia homeostazis

90

SenarCunebisaken organizmSi. lipidebis arseboba sisxlSi astimulirebs

endoTelis hemataqsikuri faqtoris sekrecias, romelic xels uwyobs

monocitebis “gamoTesvas” sisxlidan, monocitebi Tavis mxriv amzadeben

endoTelis zedapirs monocitebis adheziisaTvis. swored am jaWviT aris

warmodgenili kompensatorul SeguebiTi reaqcia, romelic mimarTulia

“skvenjer” ujredebis mosazidad sisxlZarRvis kedelSi, romlebic

monawileoben lipidebis katabolizmSi.

eleqtronul-mikroskopuli da eleqtroნul-radioavtografiuli

kvlevis monacemebi amtkiceben, rom aloqsanuri diabetis dros gvxvdeba

gansxvavebuli simwifis da funqciuri aqtiვobis makrofagebi, limfocitebi,

plazmocitebi, fibroblastebi. am ujredebis funqciuri mdgomareoba da

raodenobrivi cvlilebebi dakavSirebulia aloqsanuri diabetis

simZimesTan. diabetis progresirebis Sesatyvisad aRiniSneba makrofagebis

raodenobis Semcireba; mwife H3-uridiniT moniSnuli fibroblastebis

raodenobis zrda, saTanadod kolagenis intensiuri warmoqmna, dnm-ze da

rnm-ze moniSnuli limfocitebis raodenobis zrda, rac rogorc Cans

ganpirobebulia adgilobrivi imunuri reaqciebis rRveviT.

Saqriani diabetis dros mniSvnelovan Teoriul da praqtikul interess

warmoadgens pankreasis kunZulebSi mimdinare β-ujredebis aRdgeniTi

procesebi. cnobilia, struqturul doneze insularuli ukmarisobis

kompensacia ZiriTadad ori gziT xorcieldeba:

1) hormonoproduqciis gaZlierebiT darCenili β-ujredebis funqciuri

aqtivobis gazrdis xarjze (19, 46, 47, 69) da

2) insularuli ujredebis proliferaciis gziT. Tumca ki, isic unda

iTqvas, rom diabetis dros β-ujredebis proliferacia mniSvnelovnad

CamorCeba maTi dazianebis xarisxs.

amJamad β-ujredebiს naklovanebis Sesavsebad ganixileba ori ZiriTadi

mimarTuleba:

1) β-ujredebis miReba in vivo da Semdgom transplantacia (66, 176).

2) β-ujredebis masis zrda (45, 58, 117, 177).

dResdReobiT, regeneraciuli medicinis mizania mravali daavadebis

samkurnalod, TerapiaSi gamoiyenos zrdasruli cxovelebis organoSi

arsebuli gardamavali tipis winamorbedebi da Rerovani ujredebi (70, 81,

91

93). axali kvlevebisa da hipoTezebis safuZvelze gamoyofilia β-ujredebis

aRdgenis gansxvavebuli gzebi:

1. arsebuli β-ujredebis proliferacia, replikacia da regeneracia (52, 53,

58, 60, 117, 178).

2. pankreasis sadinrebis epiTelis neogenezi da diferenciacia (63, 72, 74,

75, 79).

3. kunZulSida arsebuli ujredebis neogenezi (86-88).

4. pankreasis diferencirebuli ujredebis acinaruli, sadinrovani,

Rerovani ujredebis da pankreasis gareT arsebuli ujredebis

transdiferenciacia (77, 80, 83, 143, 150, 151, 154, 155, 179).

ujredebis generaciis sakiTxi winamorbedi ujredebidan sakmaod

sakamaToa da gansxvavebuli. didi xnis ganmavlobaSi mecnierebi

varaudobdnen, rom mxolod embrionul Rerovan ujredebs gaaCniaT

sxvadasxva tipis qsovilebis Seqmnis unari. embrionuli Rerovani ujredebis

diferenciacia β-ujredebSi mniSvnelovani midgomaa β-ujredebis wyaros

Sesaqmnelad. seriozuli Zalebi (6, 97, 109, 180) iyo mimarTuli embrionuli

Rerovani ujredebis diferenciaciiT mieRoT β-ujredebi. Tagvebis da

adamianis embrionis Rerovan ujredebTan muSaobam aCvena, rom embrionis

Rerovani ujredebidan β-ujredebis namdvili fenotipis miReba Znelia.

Tumca cxovelebis pankreasSi aRmoCenili iyo Rerovani winamorbedebi,

romlebic formirdebodnen β-ujredebSi stimulaciis Semdeg. winamorbedebi,

romlebic miRebuli iyo embrionidan warmoadgendnen namdvil Rerovan

ujredebs, maSin rodesac winamorbedebi zrdasruli virTagvebის

pankreasidan warmoadgendnen dediferencirebul ujredebs (91, 96, 98, 111).

rigi avtorebis azriT (55, 56, 74, 86, 90, 181, 182) cxovelebis pankreasSi

aRmoCenili winamorbedebi formirdebian β-ujredebSi sadinrebis

epiTelidan, acinaruli ujredebidan, kunZulebSi arsebuli sxva

endokrinuli ujredebidan da pankreasis gareT arsebuli sxva organoebis

ujredebidan (RviZli, nawlavis epiTeli, Zvlis tvini). interess moklebuli

ar aris is faqti, rom arapankreasis warmoSobis diferencirebulma

ujredebma SeiZleba awarmoon insulinis eqspresia pankreasis

transkripciuli faqtorebis gamoyenebis Semdgom (59, 69, 118, 119, 155, 183).

92

kvlevis safuZvelze aloqsanis Seyvanidan ukve 1 Tvis Semdeg

pankreasSi gamovlenili iyo kunZul gareT arsebuli gardamavali tipis

ujredebi. es ujredebi mdebareoben kunZulebTan axlos da amave dros

uSualo SexebaSi imyofebian acinozur da sadinrovan ujredebTan. naxevrad

Txel anaTalebze sazRvari acinarul da gardamavali tipis ujredebs

Soris mkveTradaa gamoxatuli. Catarebuli dakvirvebis safuZvelze

SeiZleba davuSvaT, rom aloqsanuri diabetis dros gardamavali tipis

ujredebi gvxdeba kunZul gareT, erT wilSi SeiZleba iyos 1-2 aseTi

ujredi. gardamavali tipis ujredebi vlindeba aloqsanuri diabetis

saSualo simZimis paTologiuri procesis dros da ar vlindeba mZime

formiს SemTxvevaSi. moyvanili faqti gvaZlevs safuZvels CavTvaloT es

ujredebi kompensaciur adaptaciuri procesis gamoxatulebad aloqsanuri

diabetis dros. swored amitom, kompensaciur adaptaciuri procesebis

Seswavlisas mniSvnelovan yuradRebas iqceven gardamavali tipis insulinis

granulebis Semcveli ujredebi da maTi lokalizacia.

pankreasis kunZulebis β-ujredebis generacia rogorc Cans xdeba

cxovelebis (Tagvi, virTagva, bocveri) pankreasSi arsebuli

winamorbedebisagan sxvadasxva stimulatorebis gamoyenebis Sedegad (67, 123,

125, 130, 132, 184, 185). kerZodEglukagonis msgavsi peptidebi, eqsedin-4,

gastrini, zrdis faqtorebi, aqtivin-A, betacelulini es is nivTierebebia,

romlebsac SeuZliaT β-ujredebis regeneraciis gaZliereba. momavalSi

swored, es iqneba axali mimarTuleba Saqriani diabetis mkurnalobis

sferoSi. cxovelebis pankreasSi myofi winamorbedebisagan pankreasis

ujredebis regeneracias Tagvebsa da virTagvebSi pankreasis sxvadasxva

dazianebis Semdeg aseve aRniSnaven rigi mklevarebisa (92, 186, 187).

β-ujredebis winamorbedebisa da Rerovani ujredebis stimulirebis

mizniT Cvens mier gamoyenebuli iyo biologiurad aqtiuri nivTiereba

plaferoni (amnioturi peptidi), preparati romelic miRebulia placentiს

amnioturi garsidan da xasiaTdeba imunomamodulirebeli, anTebis

sawinaaRmdego, antioqsidaturi, antivirusuli, antiapopturi,

hipoglikemiuri TvisebebiT. plaferonis zemoqmedebis Semdeg gansakuTrebul

yuradRebas ipyrobs gardamavali tipis erTmaneTisagan gansxvavebuli

ujredebi. am gardamavali tipis ujredebs pankresaSi aqvT gansxvavebuli

93

lokalizacia. es ujredebi imyofebian diferenciaciis da simwifis

sxvadasxva xarisxSi da mdgomareobSi. eleqtronul-mikroskopuli kvleviT

rig sadinrebis epiTelur ujredebSi gamovlenilia insulinis granulebi.

imunohistoqimiuri kvleviT sadinrebis epiTelur ujredebis citoplazmaSi

aRiniSneba CK 19-is Zlieri eqspresia, xolo kunZulebTan axlos arsebuli

sadinrebis erTeuli epiTeluri ujredebi iRebebian aseve anti insulinze.

rogorc Cans plaferoni aaqtiurebs sadinrebis ujredebis specifiur gens,

Zlierdeba am ujredebis proliferacia da Sesabamisad CK 19-is eqspresia.

Cven veTaxmebiT im avtorebis (76, 188, 189) azrs, romlebic β-ujredebis

winamorbedebad miiCneven pankreasis sadinrebis epiTelur ujredebs.

savaraudoa, rom moumwifebeli ujredebi sadinrovani fazis gavliT

gadadian diferencirebul β-ujredebSi. amgvarad, rogorc Cans plaferoni

aaqtiurebs β-ujredebis neogenezs sadinrovani ujredebidan. eleqtronul-

mikroskopuli kvlevis safuZvelze Cven mier gamovlenili iyo aseve

erTeuli acinaruli ujredebi, romlebic atareben rogorc acinarul, aseve

β-ujredebis niSan Tvisebebs. eleqtronogramaze zog ujredSi insulinis

granulebis raodenoba mcirea, zogierTSi ki bevri. gardamavali tipis

ujredebis polusi, romelic miqceuli iyo kunZulisaken Seicavs β-

ujredebisaTvis damaxasiaTebel granulebs, mkveTrad gamoxatuli garsiT,

mkvrivi guliT da asimetriuli naTeli arSiiT. citoplazmis es monakveTi

dabali eleqtronuli simkvrivisaa, vinaidan is Tavisufalia

organelebisagan. marcvlovani endoplazmuri badis cisternebs ar gaaCniaT

egzokrinuli ujredebisaTvis damaxasiaTebeli paraleluroba da

warmodgenili arian vezikulebiT da erTmaneTSi gadaxlarTuli mokle

cisternebiT, mcire raodenobiTaa ribosomebi. zogierT ujredSi

marcvlovani endoplazmuri badis retikulumi vlindeba CanarTis saxiT,

swored am ubnebSi didi raodenobiTaa β-insulocitebis granulebi.

mitoqondriebi wvrilia, Seicavs erTeul kristebs da naTel matriqs, rac

damaxasiaTebelia aseve β-ujredebisaTvis. citoplazmis sxva ubnebSi

SenarCunebulia marcvlovani endoplazmuri badis cisternebis

paraleluroba. amave dros mitoqondriebi msxvilia, momrgvalo-ovaluri

formis, eleqtronulad mkvrivi matriqsiT da mravalricxovani kristebiT,

aqve vlindeba zimogenuri granulebi e.i. yvelaferi is rac axasiaTebs

94

egzokrinul ujredebs. ეleqtronogramaze nawili ujredebisa

moTavsebulia acinusebTan axlos da Seicavs pankreasis kunZulebis β-

ujredebisaTvis damaxasiaTebel granulebs. Ees granulebi imyofebian an

perinuklearul zonaSi an kidev ujredis erT-erT polusTan. zog aseT

gardamavali tipis ujredSi insulinis granulebis gverdiT moTavsebulia

zimogenuri granulebi. am ujredebis birTvs aqvs gardamavali (Sualeduri)

agebuleba, kerZod qromatinis masaSi sWarbobs euqromatini.

imunohistoqimiuri kvleviT zogierTi aseTi ujredi iRebeba anti

insulinze. Cven aseve viziarebT im avtorebis (80, 143, 150). azrs, romlebic

miuTiTeben acino insularul transdiferenciaciis SesaZleblobaze.

pankreasis kunZulebSi iSviaTad vlindeba gardamavali tipis

ujredebi, romelic erTdroulad Seicavdnen Aα-ujredisaTvis

damaxasiaTebel glukagonis da β-ujredebisaTvis damaxasiaTebel erTeul

insulinis granulebs.

pankreasis kunZulebis β-ujredebis winamorbedebis warmoSobaze da

bunebaze arsebuli kvlevebi urTierTsawinaaRmdegoa, problematuria da

dResac warmoadgens diskusiis sagans. mTeli rigi avtorebis (73, 86, 95, 151,

190). mierKkargad aris aRwerili da dokumentirebuli β-ujredebis

neogenezi sadinrebis epiTelidan, acino-insularul transdiferenciaciaze

miuTiTeben rigi mkvlevarebi (151, 154, 191), zogi avtori (87, 88) β-ujredebis

potenciur wyarod miiCnevs TviT kunZulebSi arsebul endokrinul

ujredebs. pankreasis kunZulebis endokrinul ujredebs Soris glukagonis

warmomqmneli ujredebi aris pirveli endokrinuli ujredebi, romlebic

ganicdian diferenciacias da transformacias insulinis warmomqmnel

ujredebSi (86). zogierTi mkvlevaris (52, 53, 58, 117) azriT β-ujredebis

warmoqmna xdeba kunZulebSi fakultaturi ujredebis proliferaciiT da

replikaciiT. epiTelur mezenqimur gardaqmnaze weren rigi avtorebisa (95,

157, 179, 192).

amgvarad Cveni monacemebi emTxveva im mkvlevarebis (47, 81, 156) azrs,

romlebic miuTiTeben gardamavali tipis β-ujredebis winamorbedebis

arsebobaze pankreasSi. es ujredebi imyofebian funqciurad mosvenebul

mdgomareobaSi rogorc paTologiis, ise fiziologiis pirobebSi da am

gardamavali tipis ujredebidan Sesaძlebelia endokrinuli ujredebis

95

warmoqmna stimulaciis Semdeg, Tumca ki zogierTi avtori (70, 91, 93) β-

ujredebis winamorbedebad miiCnevs damoukidebel Rerovan ujredebs,

romlis funqcia jer kidev gaurkvevelia.

Catarebuli dakvirvebis safuZvelze SeiZleba davuSvaT, rom

aloqsanuri diabetis dros β-ujredebis niSan-Tvisebebis mqone gardamavali

tipis ujredebi gvxdeba rogorc kunZul gareT aseve kunZulebSic.

pankreasis sadinrovan, acinarul da kunZulebis rig endokrinul ujredebs

da Rerovan ujredebs aqvT unari neogenezis, replikaciis, diferenciaciis,

transdiferenciaciis gziT gardaiqmnan β-ujredebad rigi stimulatorebis,

Cvens SemTxvevaSi plaferoniT zemoqmedebis Semdeg. swored

mastimulirebeli faqtorebis gamoyeneba zrdasruli cxovelebis pankreasSi

arsebuli winamorbedebis mimarT, SeiZleba gaxdes β-ujredebis masis zrdis

mizezi.

Cveni kvlevis safuZvelze plaferoniT zemoqmedebis Semdeg

gansakuTrebul yuradRebas ipyrobs izolirebulad myofi β-ujredebi. es

ujredebi ar arian organizebuli kunZulebSi. Cvens mier eqstra

insularul komponentad miRebuli iyo is ujredebi, romlebic Seicavs

insulinis mwife granulebs da romlebSiac kargad vlindeba birTvi. A

ujredebis simwifis da funqciuri aqtivobis dasadgenad Catarebulia

eleqtronul-morfometruli kvleva. miRebuli monacemebi damuSavebulia

statistikurad. daTvlilia insulinis granulebis raodenoba, naTeli da

muqi insulinis granulebis raodenoba da am granulebis procentuli

Sesabamoba, insulinis granulebis diametri da maT mier dakavebuli

sivrce. miRebul monacemebs vadarebdiT aloqsanis da sakontrolo jgufis

virTagvebis pankreasis kunZulebis β-ujredebis insulinis granulebs.

Eleqtronul-morfometrulma kvlevam gviCvena arsebuli sxvaoba daTvlil

parametrebs Soris. miRebuli monacemebis safuZvelze dadginda, rom

izolirebul β-ujredebSi aloqsanur da sakontrolo jgufTan SedarebiT

mniSvnelovnad momatebulia naTeli insulinis granulebis raodenoba. Cven

vvaraudobT, rom naTeli granulebis mateba miuTiTebs am β-ujredebis

unarze awarmoon insulinis swrafi sekrecia gansxvavebiT muqi

granulebisagan, romelTa siWarbe miuTiTebs ZiriTadad sekretis

dagrovebaze. Cven veTanxmebiT im avtorebis azrs (9, 20, 169, 193), romlebic

96

naTeli insulinis granulebis matebas β-ujredebSi ukavSireben insulinis

swraf sekrecias.

აmgvarad Cveni kvlevis safuZvelze SeiZleba vivaraudoT, romBpankreass

gaaCnia ujreduli plastiuroba da aqvs unari dasabami misces

multipotentur progenitorebs, rasac aseve aRniSnaven rigi mkvlevarebisa

(74, 135, 137, 176, 194). Cveni Sedegebi TvalnaTliv miuTiTeben, rom pankreasis

sadinrovan, acinarul, endokrinul da Rerovan ujredebs aqvT poteciali

diferencirdnen pankreasis β-ujredebSi. swored es aris pirveli nabiji β-

ujredebis regeneraciisa in vitro da warmoadgens diabetis axali Terapiuli

mkurnalobis safuZvels. plaferoni xels uwyobs pankreasSi arsebuli

winamorbedi ujredebis β-ujredebSi neogenezis, diferenciaciis,

transdiferenciaciis process. savaraudoa, rom plaferoni virTagvebis

pankreasSi astimulirebs β-ujredebis generacias winamorbedi da Rerovani

ujredebidan.

Cveni monacemebis safuZvelze SeiZleba davaskvnaT, rom arsebuli

mastimulirebeli faqtoris gamoyeneba amcirebs hiperglikemias, magram ar

dahyavs glukoza miRebul normamde. vaCvenebT ra β-ujredebis

winamorbedebis arasrulfasovnebas gamoimuSaon insulinis sakmarisi

raodenoba vvaraudobT, rom arsebuli midgomis SezRuduli

SesaZleblobebi SeiZleba gamowveuli iyos Semdegi mizezebiT:

1) diferencirebuli ujredebis arasruli dediferenciacia winamorbed

ujredebis mgomareobamde;

2) dediferencirebuli winamorbedebis arasakmarisi rediferenciacia β-

ujredebSi;

3) insulinis mwarmoebul ujredebis SezRuduli unari, awarmoon

proliferacia da momwifdnen glukozaze moreagire ujredebis donemde. P

plaferoni aseve garkveul gavlenas axdens mikrovaskularul

kalapotSi mimdinare cvlilrbebze. plaferoniT zemoqmedebis Semdeg

virTagvebis pankreasis kunZulebis sinusoidebSi endoTeli Txelia,

fenestrirebuli. Cveni varaudiT plaferoni aZlierebs antioqsidaciur da

antiinflamaciur procesebs, aregulirebs oqsidaciur metabolizms

vaskularul sistemaSi, aRadgens redoqs damokidebul nitrit oqsidebis

aqtivobas da amcirebs sinusuri kapilarebis endoTelis dazianebis

97

xarisxs. zog monakveTebSi endoTeli ganicdis Zlier proliferacias.

Cndeba axlad warmoqmnili sisxlZarRvebi. eleqtronul-

radioavtografiuli kvleviT am monakveTebSi endoTeli aqtiurad

moiniSneba H3-TimidiniT, xolo imunohistoqimiuri kvleviT kunZulebis

kapilarebis endoTelis citoplazmaSi aRiniSneba CD 34-is Zlieri eqspresia,

rac miuTiTebs angiogenezis procesis mkveTr zrdaze. CD 34-is mimarT

pozitiuri ujredebi gabneulia mTel pankreasSi. rac Tavis mxriv mianiSnebs

Zvlis tvinis warmoSobis Rerovani ujredebis mobilizaciis aqtivaciaze.

plaferonis zemoqmedebis Semdeg kunZulebis perikapilarul sivrceSi

aRiniSneba fibrozuli CanarTebis Semcireba. Cveni varaudiT es gamowveulia

makrofagebis aqtivaciiT. rogorc Cans plaferonis zemoqmedebiT, izrdeba

lizosomebis enzimebiT eqskreti da Sesabamisad Zlierdeba boWkoebis

lizisi.

amgvarad aSkaraa, rom ZiriTad moments, romelic ganapirobebs

daavadebis manifestacias, misi mimdinareოbis simZimes aris pankreasis

kunZulebis β-ujredebis dazianebis xarisxi. kvlevis Sedegebis analizi

saSualebas gvaZlevs davadginoT, rom aloqsanuri diabetis dros

pankreasis kunZulebSi aRiniSneba ujredebis Zlieri destruqcia, nekrozi

da apoptozi, romlis paTogenur safuZvels warmoadgens cvlilebebi

mikrocirkulaciur sistemaSi (endoTelis distrofia, deskvamacia,

Camofcqvna da sxva) endoTeluri Sris barieris moSlas, mosdevs anTebiTi

da imunuri ujredebis (makrofagebis, limfocitebis, plazmocitebis)

migracia perikapilarul sivrceSi da kunZulebSi. aqtiuri, mwife

fibrolastebis gaCena, rac Tavis mxriv aZlierebs ujredebis dazianebis

xarisxs. amgvarad aloqsanuri diabetis dros viTardeba

urTierTganpirobebuli progresirebadi cvlilebebi mikrocirkulaciur

wreSi da β-ujredebSi. am morfologiuri cvlilebebis gamoxatuleba

pirdapir kavSirSia paTologiuri procesis simZimesTan.

aloqsanuri diabetis dawyebidan 1 Tvis da 10 dRiani plaferonis

kursis Semdeg virTagvebis sisxlSi glukozis Semcveloba mcirdeba 50-60

mg%iT. virTagvebis pankreasis kunZulebSi mniSvnelovani cvlilebebi ar

aRiniSneba. plaferoniT zemoqmedebis Semdeg virTagvebis pankreasis

kunZulebSi nekrobiozuli cvlilebebis paralelurad gvxdeba

98

hipertrofuli kunZulebi erTeuli ujredebiT, romlebSiac aRiniSneba

mitozebi. vizualurad Semcirebulia apoptozuri ujredebiს raodenoba.

plaferoni, rogorc Cans icavs pankreasis qsovils dazianebisagan, romelic

gamowveulia aloqsaniT. plaferoni awarmoebs pro-inflamatoruli

citokinebis sinTezis da Tavisufali radikalebis reproduqciis

inhibirebas. savaraudoa, rom plaferoni gvevlineba β-ujredebis damcvelad,

awarmoebs ra mitoqondriuli potencialis aRdgenas, aZlierebs β-ujredebis

proliferacias, misi mitogenuri aqtivobis gazrdiT (165). aloqsaniT

dazianebul virTagvebis pankreasSi plaferoni xels uwyobs β-ujredebis

generacias winamorbedi da Rerovani ujredebidan, Tumca ki ver axerxebs

insulinis deficitis srul kompensacias organizmSi. Kplaferoni Tavisi

antioqsidaciuri da antiinflamaciuri TvisebebiT axdens metabolizmis

stabilizacias mikrocirkulaciur sistemaSi da amcirebs endoTelis

dazianebis xarisxs sinusoiduri tipis kapilarebSi. aloqsaniT dazianebul

virTagvebis pankreasSi plaferoni xels uwyobs β-ujredebis generacias

winamorbedi da Rerovani ujredebidan, Tumca ki ver axerxebs insulinis

deficitis srul kompensacias organizmSi. K

Ealoqsanuri diabetis dros mamr virTagvebis sisxlSi aRiniSneba

adaptaciuri hormonebis kortikosteronis da somatotropinis plazmuri

koncentraciis zrda, aromatizaciis procesebis aqtivacia, testosteronis

koncentraciis Semcireba, gamowveuli misi aromatizaciis aqtivaciiT,

estradiolis raodenobis momateba, dnm-isa da rnm-is sinTezis Semcireba.

rogorc Cans, aloqsanuri diabetis dros mamr virTagvebSi xdeba

metaboluri da hormonuli TviTregulaciis moSla, romelic vlindeba

metaboluri stresis saxiT.

sinTezuri radioinertuli androgen- meTiltrieნolonis yoveldRiuri

or kviriani kursis Semdgom mamr virTagvebis sisxlSi, aloqsanur diabetis

virTagvebis sisxlSi arsebul monacemebTan SedarebiT, aRiniSneba

glukozis koncentraciis Semcireba, rac rogorc Cans ganpirobebulia

qsovilebis insulinisadmi mgrZnobelobis gazrdiT. kortikosteronisa da

somatotropinis koncentraciis Semcireba, aromatizaciis procesebis

Seneleba, estradiolis da testosteronis koncentraciis zrda da

miaxloeba normasTan, dnm-isa da rnm-is sinTezis aqtivacia, pankreasis

99

kunZulebSi – ujredebis proliferaciis aqtivacia. testosteronis

plazmuri koncentaciis miaxloeba normasTan xels uwyobs pankreasSi

aqtiuri androgen receptorebis gajirjvebas testosteroniT, rasac

mosdevs Tavisufali receptorebis Semcvelobis Semcireba. testosteronis

citoproteqtuli efeqti, rogorc Cans dakavSirebulia antioqsidaciuri

enzimebis induqciasTan β-ujredebSi. literaturuli monacemebiT (10, 160)

sasqeso steroidebis moqmedebis meqanizmi mdgomareobs maT

urTierTqmedebaSi cilovan receptorebTan, steroid receptoruli

kompleqsis translokaciaSi birTvSi da maT urTierTqmedebaSi birTvis

qromatinis aqceptorebTan. Sedegad xdeba birTvis qromatinis struqturis

Secvla, transkripciis da ujreduli cilebis sinTezis Secvla, romlebic

Tavis mxriv aCqareben kompensatorul procesebs. Aamgvarad Cveni varaudiT

androgenebi iReben monawileobas organizmSi mimdinare metabolur da

kompensatorul procesebSi. androgenuli regulaciis efeqturoba

ganisazRvreba rogorc hormonis koncentraciis SemcvelobiT, aseve

ujredebSi androgenuli receptorebis doniT. miRebuli monacemebi emTxveva

rigi mkvlevarebis azrs (161, 162) androgenebis regulatorul moqmedebaze

sqesiT diferencirebul cxovelebSi mimdinare adaptaciur procesebze.

kvlevis safuZvelze pankreasSi gamovlenili parenqimul-stromuli

elementebis urTierTdakavSirebuli cvlilebebi safuZvels gvaZlevs

vimsjeloT ara marto paTologiur Zvrebze, aramed im kompensaciur-

adaptaciur procesebzec, romelic viTardeba virTagvebis pankreasSi

aloqsanuri diabetis dros, plaferoniTa da sinTezuri radioinertuli

androgen-meTiltrieნolonis zemoqmedebis Semdeg.

100

დასკვნა

1. Seswavlilia β-ujredebis morfo-funqciuri suraTi aloqsanuri

diabetis ganviTarebis da Camoyalibebis procesSi. dadgenilia, rom es

cvlilebebi aris Saqriani diabetis klinikuri gamovlinebis ZiriTadi

morfologiuri maCvenebeli da asaxavs aloqsanuri diabetis rogorc

simZimes, ise stadias. es morfologiuri maCvenebeli damokidebulia

glukozis Semcvelobaze sisxlSi.

2. gamovlenilia urTierTdamokidebuleba erTis mxriv B β-insulinis

warmomqmnel ujredebs da meores mxriv glukagonis da somatostatinis α

da δ ujredebs Soris. dadgenilia, rom aloqsanuri diabetis dros,

pankreasis endokrinuli nawili naxSirwylebis cvlis moSlaze

kompleqsurad pasuxobs misi yvela komponentebis met-naklebi

monawileobiT.

3. aloqsanuri diabetis dros pankreasSi gamovlenilia multipotenturi

progenitorebi. es ujredebi moTavsebulia sadinrebTan da acinusebTan

axlos da atareben, rogorc pankreasis acinaruli, sadinrebis epiTelis

da kunZulSida endokrinuli ujredebis, aseve Bβ-ujredebis niSan

Tvisebebs. kvlevebiT dadgenilia, rom eqsperimentuli diabetis

pirobebSi es gardamavali tipis ujredebi imyofebian mosvenebul

mdgomareobaSi, razedac miuTiTebs maTSi arsebuli sekretoruli

granulebis simwifis xarisxi.

4. aloqsanuri diabetis dros virTagvebis pankreasSi aRiniSneba

urTierTganpirobebuli, progresirebadi cvlilebebi mikrocirkulaciur

wreSi (enoTelis distrofia, deskvamacia, fenestrebis raodenobis

101

Semcireba) da sxvadasxva xarisxis dazianebebi pankreasis kunZulebis β-

ujredebSi (distrofia, nekrozi), am morfologiuri cvlilebebis

gamoxatuleba pirdapir kavSirSia aloqsanuri diabetis simZimesTan.

5. pankreasis kunZulebis SemaerTebel qsovilSi gamovlenili cvlilebebi

(kunZulebSi uxeSi fibrozuli boWkoebis gaCena, kunZulebis struqturis

rRveva) histio-limfocitaruli infiltracia perikapilarul sivrceSi

da kunZulebSi zrdis β-ujredebis dazianebis xarisxs paTologiuri

procesis simZimis proporciulad.

6. aloqsanuri diabetis dros pankreasis kunZulebSi Tanmimdevrulad

ganviTarebuli cvlilebebi uSualo kavSirSia paTologiuri procesis

simZimesTan, es ki saSualebas gvaZlevs mkveTrad ganvsazRvroT β-

ujredebis dazianebis xarisxi, gamovyoT Seqcevadi cvlilebebi

Seuqcevadisagan, rasac TeoriulTan erTad aqvs didi praqtikuli

mniSvneloba. miRebuli monacemebis safuZvelze SeiZleba davaskvnaT, rom

aloqsanuri diabetis dros qsovilovan doneze moqmedebs meqanizmebi,

romlebic avtomaturad uzrunvelyofen parenqimisa da stromis

urTierTregulacias.

7. plaferoniT zemoqmedebis Semdeg klebulobs glukozis koncentracia

virTagvebis sisxlSi. adgili aqvs sklerozuli procesis Seqcevadobas,

kerZod, fibrozuli Sreebis rezorbacias (aseT ubnebSi Warbadaa

makrofagebi). miRebuli monacemebis safuZvelze SeiZleba davaskvnaT, rom

plaferoni aaqtiurebs makrofagebs. makrofagebis mier gamoyofili

lizosomuri fermentebiT xdeba kolagenuri boWkoebis lizisi, rac

Tavis mxriv xels uwyobs sekretis gadaadgilebas sisxlZarRvis

sanaTurSi da warmoadgens kompensaciur adaptaciuri procesesis

gamovlinebas.

102

8. plaferoniT zemoqmedebis Semdeg pankreasis kunZulebSi da kunZul

gareT vlindeba gardamavali tipis ujredebi mkveTrad gamoxatuli β-

ujredebis niSanTvisebebiT. am gardamavali tipis ujredebs aqvT maRali

sekretoruli aqtivoba da maTSi ar aRiniSneba destruqciuli

cvlilebebi. miRebuli Sedegebis safuZvelze SeiZleba davaskvnaT, rom

gardamavali tipis ujredebs aqvT potencia neogenezis, diferenciaciis

da transdiferenciaciis gziT diferencirdnen pankreasis β-ujredebSi

stimulaciis Semdeg.

9. virTagvebis aloqsan-plaferonis jgufSi gamovlenilia izolirebuli β-

ujredebi. es ujredebi ar arian organizebuli kunZulebSi. am β-

ujredebis mier gamoyofili sekreti aumjobesebs, magram ar dahyavs

normamde glukozis raodenoba sisxlSi. plaferoni amcirebs

hiperglikemias, Tumca ki ver axerxebs insulinis deficitis

kompensacias organizmSi.

10. amgvarad pankreasis sadinrebis epiTelur, acinarul da rig endokrinul

da Rerovan ujredebs gaaCniaT ujreduli plastiuroba da SeuZliaT

diferencireba pankreasis kunZulebis β-ujredebSi plaferonis

zemoqmedebiT.

11. androgenebi iReben monawileobas organizmSi mimdinare metabolur da

kompensatorul procesebSi. androgenuli regulaciis efeqturoba

ganisazRvreba rogorc hormonis koncentraciis SemcvelobiT, aseve

ujredebSi androgenuli receptorebis doniT.

103

12. arsebuli monacemebi saSualebas mogvcems momavalSi pankreasis

endokrinuli nawilis potenciuri saSualebebis gamoyenebiT

gamovimuSaoT mkurnalobis axali alternatiuli meTodebi.

104

SUMMURY

The ability of dysfunctional β-cell lesions to regulate blood glucose levels can be normalized in by

increasing the mass of existing β-cells in the pancreas. This approach can be achieved by the

regeneration, proliferation, and replication of pre-existing β-cells, as well as by the neogenesis of β-

cells from precursor, stem cells or by trans-differentiation from other differentiated cells.

In the present study we induced alloxan diabetes in experimental animal model and studied the

influence of Plaferon LB (amniotic derived peptide) and radio-inert synthetic androgen

methyltrienolon on renewal processes of the pancreas. Histological, electrono-microscopical,

immunohistocemical, electron-morphometrical and radio-immune methods in the pancreases of rats

with alloxan-induced diabetes were studied. From a total of 120 Wistar laboratory rats, 30 received

an alloxan injection to induce diabetes and were treated one month later with Plaferon LB (0.25

mg/g) (Alloxan/Plaferon LB-treated group). Thirty male rats with Alloxan diabetes were treated one

month later with radio-inert synthetic androgen methyltrienolon and rats with Alloxan diabetes

received an alloxan injection but no subsequent treatments (Alloxan-treated group), and a control

group of 30 rats (Control group). The blood glucose level was used as a marker for Alloxan-induced

diabetes. Pieces of pancreas were sampled and tissue morphological analysis was undertaken after

cessation of experiment.

In Alloxan-treated group, changes such as dystrophy and necrosis were apparent not only in the β-

cells but also in the vascular system of the pancreatic islets. During the development of alloxan-

induced diabetes in our study, the endothelium underwent alterations (dystrophy and desquamation

of the endothelium) followed by the transendothelial migration of immune and inflammatory cells

(macrophages, lymphocytes, plasmocytes,) into the pericapillary space and the endocrine tissues,

with consequent progressive injury of the β-cells. Alloxan/Plaferon LB-treated group presented

endothelial layers that appeared thin and well-fenestrated, having pericapillary spaces without

fibrous inclusions.

Based on our findings, we suggest that Plaferon LB exerts antioxidant and anti-inflammatory

effects, stabilizing oxidative metabolism in the vascular system and decreasing the intensity of

injury in the endothelium of the sinusoidal capillaries. In Alloxan/Plaferon LB-treated group, extra

islet transitional cells were observed containing granules with varying degrees of maturation and

105

exhibiting features specific for insulin-secreting β-cells. Immunohistochemical analyses showed

that CD 34 positive cells were located within islets and scattered throughout pancreas. Endothelial

cells of islet sinusoidal capillaries strongly expressed by CD 34. According to this finding we

hypothesized that Plaferon LB activates processes of endothelial proliferation and initiates

formation of new capillaries. Subpopulations of cells adjacent to the ductal epithelium contained

CD 34 positive precursor cells and perhaps giving rise to β-cells. Evidently in diabetic rats pancreas

Plaferon LB activate angiogenic processes and mobilization of bone marrow- derived cells. In

Alloxan/Plaferon LB-treated group immunohistochemical analysis also revealed strong expression

of Cytokeratin 19 (CK19) in the duct cells nearby pancreas islets, we support the idea that β-cell

progenitors go through a ductal phase from an immature to an adult β-cell. Plaferon LB as it seems

activated neogenesis of β-cells from duct cells. Electron-microscopic findings suggest that β-cell

precursors are not restricted to only pancreatic ducts, and generate also through acino-insular trans-

differentiation. In the present study single acinar cells including insulin granules were manifested in

the ducts near the islets. We agree with opinion of some authors specifying on a possibility of

acino-insular transdifferentiation from exocrine tissue. Electrono-morphometric analysis of insulin

granules in the extra-islet isolated β-cells showed increased proportion of light granules which is

associated with increased insulin secretion. Present results suggest that Plaferon LB:

Promotes a decrease in the blood glucose level;

Helps to stabilize oxidative metabolism in the vascular system and to decrease the intensity

of endotheliocyte injury;

Encourages the maturation and differentiation of transitional precursor cells;

Induces the renewal of β-cells in the pancreas of rats with alloxan-induced diabetes.

Treatment with Plaferon LB appears to enable the damaged pancreas to generate new β-cells

The two-week everyday application of radio-inert synthetic androgen methyltrienolon caused in

male rats with Alloxan diabetes sharp increase of testosterone concentration in blood serum (92 %

from 52 % initial) and was accompanied with decrease in glucose concentration (43 % from initial)

due to the increased sensitivity of tissues to insulin. Testosterone active androgen receptors in the

pancreas islet, reducing the content of free receptors to 121 % with control indicators equal to 210

%. Testosterone has an inhibitory effect on the catabolic action of glucocorticoids and improves

state of β-cells which was confirmed by radiometry showing an increase of DNA and RNA in these

106

animals compared with the control of DNA synthesis by 16 % and 12 % RNA. These findings are

consistent with the opinion of some authors about regulatory effects of androgens on sex-

differentiated and adaptive responses of the male body. Our results suggest that in Alloxan/Plaferon

LB-treated group extra- and intra-islet transitional cells exist in a resting condition and can

differentiate into β-cells. Based on the properties we observed in these transitional cells, we

conclude that subsets of these cells were derived from acinar, ductal, and endocrine cells, or even

from non-differentiated stem cell. Presumably, Plaferon LB stimulates the maturation and

differentiation of β-cell precursors and participates in the renewal process of β-cells in the diabetic

rat’s pancreas. When radio-inert synthetic androgen methyltrienolon caused in male rats with

Alloxan diabetes stimulate proliferation of pancreas islets β-cells. However the effect of Plaferon

LB and radio-inert synthetic androgen methyltrienolon are not sufficient to compensate for insulin

deficiency.

107

გამოქვეყნებული შრომების სია

1. Extra-islet intermediate cells of pancreas and effect of Plaferon in Alloxan induced diabetes

mellitus. Bulletin of the Georgian National Academy of Sciences 2009, 3, 3:169-172.

Latsabidze I. Machavariani T. Gachechiladze I. Gvamichava T. Kavtiashvili K.

2. virTagvas pankreasis kunZulebSi mimdinare morfologiuri

cvlilebebi aloqsanuri diabetis dros da plaferoniT

zemoqmedebisSemdeg. eqsperimentuli da klinikuri medicina 2010; 3 (58);

12-15. i.lacabiZe.

3. Beta-cells of Rats Pancreas and their Supposed Precursors during Alloxan Diabetes and

after the Action of Plaferon LB. Georgian Medical News, 2011, 9,198:40-45.

Latsabidze I. Machavariani T. Gachechiladze I. Gvamichava T. Kavtiashvili K.

4. virTgvebis pankreasis kunZulebis mikrocirkulaciur wreSi

ganviTarebuli struqturuli cvlilebebi aloqsanuri diabetis

dros. eqsperimentuli da klinikuri medicina 2014; 1, 34-36. i.lacabiZe,

T.maWavariani, i.gaCeCilaZe, T.RvamiCava.

5. virTagvebis pankreasSi ganviTarebuli ultrastruqturuli

cvlilebebi aloqsanuri diabetis dros. eqsperimentuli da

klinikuri medicina 2014; 5, 60-62. i.lacabiZe, T. maWavariani,

T.RvamiCava, i.gaCeCilaZe.

6. Корекция гормонально-метаболических нарушений у самцов крыс с

развивающимся экспериментальным диабетом. Бюлетень Экспериментальной

Биологии и Медицины. Изд. Росс. Акад. Мед. Наук 2015 Том 159, № 1 ЯНВАРЬ.

Н.А. Дидебулидзе, М.Ш. Какабадзе Н.Г. Гордадзе И.Н. Лацабидзе М.Э.

КордзаяИ.Т. Сихарулидзе.

108

ლიტერატურა

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