FsaqarTvelos mecnierebaTa akademiis al. naTiSvilis saxelobis
eqsperimentuli morfologiis instituti
xelnaweris uflebiT
lali SoTas asuli ruxaZe
fsoriazis morfogenezisa da klinikuri mimdinareobis
Taviseburebani nunisis mineraluri wylebis gamoyenebis pirobebSi
avadmyofobis kompleqsuri mkurnalobis dros
14.00.11 _ kanisa da veneruli sneulebani
medicinis mecnierebaTa kandidatis samecniero xarisxis
mosapoveblad warmodgenili
d i s e r t a c i a
samecniero xelmZRvaneli: al. kacitaZe
med. mec. doqtori, profesori
samecniero konsultanti: z. cagareli
med. mec. doqtori, profesori
Tbilisi _ 2006 w.
sarCevi
disertaciaSi gamoyenebuli Semoklebani da abreviaturebi 4
Sesavali 6
naSormis mecnieruli siaxle 10
naSromis praqtikuli Rirebuleba 11
praqtikaSi danergva 11
sadisertacio Sromis aprobacia 11
naSromis irgvliv gamoqveynebuli publikaciebi 12
naSromis struqtura da moculoba 12
1. literaturis mimoxilva 13
1.1 fsoriazis ganviTarebis zogierTi imunologiuri da
genetikuri aspeqti
13
1.2 redoqs statusis roli fsoriazis paTogenezSi 21
1.3 apoptozi da misi roli fsoriazis paTogenezSi 34
1.4 fsiqodermatologiuri aspeqtebi fsoriazis dros 44
2. kvlevis masala da meTodebi
2.1 kurort nunisis daxasiaTeba
2.2 klinikuri masalis mimoxilva
2.3 fsoriazis simZimis xarisxis gansazRvra
54
54
56
63
2.4 sisxlis imunologiuri maCveneblebis gansazRvra 64
2.4.1 T- da B-limfocitebis raodenobrivi gansazRvra 64
2.4.2 imunoglobulinebis raodenobrivi gansazRvra 65
2.4.3 leikocitebis interferonuli reaqcia 66
2.4.4 sisxlis neitrofilebis fagocituri aqtivoba 66
2.5 sisxlis bioqimiuri maCveneblebis gansazRvra rezonansi
(epr) speqtroskopuli meTodiT
2.6 periferiuli sisxlis limfocitebis eleqtronul-
mikroskopuli da imunohistoqimiuri kvleva
67
68
2.7 fsoriaziT daavadebul pacientTa fsiqologiuri
mdgomareobis gansazRvra
70
3. gamokvlevis Sedegebi 73
2
3.1 vulgaruli fsoriaziT daavadebulTa sisxlis
imunologiuri maCveneblebis cvlilebebi nunisSi
balneoTerapiis kursis Catarebisas
75
3.2 sisxlis pro- da antioqsidanturi maCveneblebi
fsoriazis dros
78
3.3 vulgaruli fsoriaziT daavadebulTa sisxlis pro- da
antioqsidanturi sistemis cvlilebebi nunisSi
balneoTerapiis kursis Catarebisas
3.4 limfocitebis elqtronulmikroskopuli da
imunohistoqimiuri kvlevis Sedegebi nunisSi
balneoTerapiis kursis Catarebisas
82
85
3.5 vulgaruli fsoriaziT daavadebulTa fsiqologiuri
statusis cvlilebebi
91
4. miRebuli Sedegebis gansja 99
daskvnebi 108
praqtikuli rekomendaciebi 109
gamoyenebuli literatura 110
3
disertaciaSi gamoyenebuli Semoklebani da abreviatureti
-GCS - gama-glutamilcistein sinTaza
ADP - adenozindifosfati
AIF - apoptozis gamomwvevi faqtori
APAF- apoptozuri proteazas gamaaqtivebeli faqtori
APG - antigen prezentirebul ujredebTan
ATP - adenozintrifosfati
Bcl antiapoptozuri proteinebis ojaxi
CARD - kaspazas rekroitirebis domeni
CLA - limfocit-asocirebuli antigenebi
cNOS - konstituciuri NO sinTaza
COX - ciklooqsigenaza
DED - sikvdilis efeqtoris domeni
DID - sikvdilis gamomwvevi domeni
EGF - epidermuli zrdis faqtori
EPK - epidermuli regulatorul kinaza
epr eleqtronulparamagnituti rezinansi
HLA adamianis autoantigeni
IFN- - interferon-
Ig - imunoglobulinebis ojaxi
IL interleikinebis ojaxi
INF _ interferoni
iNOS - inducibeluri NO sinTaza
JNK - N-terminalur kinaza
LOO. lipidebis peroqsiradikalebi
MAP - mitogen gamaaqtivebeli proteini
Me cvalebadvalentovani metalis ioni
MHC didi histoSeTavsebadobis kompleqsi
MICA - HLA-dakavSirebuli polimorfuli antigeni
MIP-1 _ makrofagis anTebis proteini-1
4
MMP - matriqsis metaloproteinaza
NFkB - birTvuli faqtori kB
NK naturaluri kileri
nNOS - neironuli NO sinTaza
NO azotis Jangi
NOS - NO sinTazas ojaxi
O2- - superoqsidi
ONOO- - peroqsinitriti
P-53 ujredul ciklSi transkrifciis faqtori
PASI - fsoriazis simZimisa da dazianebis keris farTis indeqsi
PKC - proteinkinaza C
RNS - azotis reaqciuli naerTebis
ROS Jangbadis reaqtiuli SenaerTebi
SMAC - apoptozis gamaaqtivebeli faqtori
SOD _ superoqsiddismutaza
TCR - antigenis gamocnobaze pasuxismgebeli receptorebi
TGF- - matransformirebeli zrdis faqtori
Th - T helperi
Ts - T supresori
TIMP - specifiuri qsovilovani inhibitori
TNF- - simsivnis manekrozirebeli faqtori
5
S e s a v a l i
fsoriazis mkurnaloba Tanamedrove medicinis aqtualuri problemaa.
igi msoflioSi kanis erT-erTi yvelaze gavrcelebuli dermatozia, romlis
xvedriTi wili kanis paTologiebs Soris 1-8 procentia ( ..,
.. 1992). bolo wlebSi msoflios TiTqmis yvela qveyanaSi da
saqarTveloSic sagrZnoblad imata fsoriazis raodenobam. amerikis
fsoriazis fondis monacemebiT, am paTologiiT 5 000 000 amerikelia
daavadebuli, materialuri xarji ki Seadgens 3,5 miliard dolars
weliwadSi. yovelwliurad 200 000 axali SemTxveva registrirdeba,
romelTaganac 10% bavSvia (Dereure O, 2003).
problemis simwvaves ganapirobebs daavadebis qronikuli mimdinareoba,
ucnobi etiologia da dauzustebeli paTogenezi, xanmokle remisiebi, xSiri
recidivebi, TviTmkurnaloba, mkurnalobis tradiciuli meTodebisadmi
rezistentoba da kortikosteroidul Terapiaze damokidebul avadmyofTa
ricxvis mateba.
amasTan, iseve, rogorc sxva kanis qronikuli daavadebebi, fsoriazic
iwvevs kosmetikur cvlilebebs, rac uaryofiTad moqmedebs pacientis fsiqo-
emociur mdgomareobaze. gamokvlevebma aCvena, rom pacientTa 30%-s
axasiaTebs suicidisken midrekileba, depresia (Richards HL., et al. 2004). amis
gamo, fsoriazi ara marto mediko-biologiuri, aramed mwvave socialuri
problemac aris. yovelive zemoT CamoTvlili fsoriazis Seswavlis sakiTxs
kidev ufro aqtualurs xdis.
fsoriazis kvlevas didi xnis istoria aqvs. jer kidev Cvens
welTaRricxvamde hipokrate Tavis naSromSi `Corpus Hippocraticum~ aRwers am
daavadebas. Tumca, maSinac da dResac am daavadebis etiologia da
paTogenezi ucnobia. bevri faqti miuTiTebs, rom fsoriazi genetikuri da
garemo faqtorebis erToblivi zemoqmedebis Sedegia.
aseve didi xnis istoria aqvs fsoriazis mkurnalobas, Tumca,
ZiriTadad, igi atarebda empiriul xasiaTs paTogenezis gaTvaliswinebis
gareSe. amitom fsoriazis ganviTarebis meqanizmebis Seswavla saSualebas
mogvcems ara marto gaviRrmavoT codna daavadebis zogadbiologiuri
6
kanonzomierebis Sesaxeb, aramed SevimuSaoT mkurnalobis axali,
paTogenezze damyarebuli, meTodebi.
fsoriazi qronikuli, multifaqtoruli bunebis eriTematozul-
sqvamozuri dermatozia, romelic xasiaTdeba epidermisis bazaluri
ujredebis hiperproliferaciiT, keratinizaciis procesis darRveviT,
dermaSi anTebiTi reaqciebiT da cvlilebebiT sxvadasxva organoebsa da
sistemebSi; iwvevs kanis, misi danamatebis, lorwovani garsisa da saxsrebis
dazianebas. fsoriazs ganixilaven, rogorc sistemur daavadebas (
.., ..1999). dRemde gaurkvevelia, ra meqanizmebiT xdeba
imunitetis ujreduli rgolis gaaqtiveba, efeqtoruli T limfocitebis
raodenobis da maTi kanSi aqtivaciis momateba. varaudoben, rom am jgufis
limfocitebi informacias (signals) iReben dendrituli ujredebidan da
yalibdeba autoimunuri reaqciisaTvis damaxasiaTebeli mankieri wre, sadac
didi mniSvneloba eniWeba bazaluri da wvetiani ujredebis apoptozis
gaZlierebas. es iwvevs proliferacias, kanis limfoidur-ujredovan
infiltracias da meoTxe tipis dayovnebuli hipermgrZnobelobis imunur
reaqcias, rac arTulebs fsoriazis mkurnalobas.
ukanasknel periodSi fsoriazis etiologiis da paTogenezis Sesaxeb
dagrovda mravali Teoria, rac miuTiTebs fibroblastebis, neitrofilebis,
poxieri ujredebis, T limfocitebis, citokinebis da nervuli daboloebebis
rolze fsoriazis ganviTarebaSi. Teoriebis simravle ki problebis
sirTuleze da mravalfaqtorulobaze miuTiTebs. Tumca, yoveli Teoria
iTvaliswinebs da aRiarebs anTebisa da da autoimunuri reaqciebis wamyvan
mniSvnelobas.
bolo xanebSi gansakuTrebiT didi roli eniWeba genetikur
aberaciebs. isini nanaxia sxvadasxva qromosomebSi, romelTa umravlesoba
asocirebulia sxva autoimunur da anTebiT daavadebasTan, rogorebicaa
asTma, egzema da sxv. es miuTiTebs, rom fsoriazis etiologiaSi ar
SeiZleba wamyvani iyos romelime erTi humoruli an ujreduli faqtori.
fsoriazis paTogenezSi mniSvnelovania T limfocitebis da misi
subpopulaciebis disregulacia, rac sxva qsovilovani faqtorebis da
epidermiocitebis paTologiuri Zvrebis inicirebas iwvevs. kanis
7
epidermiocitebis disproliferaciuli da hiperkeratozuli statusis
Camoyalibeba Sedegia swored limfocitebis da biologiurad aqtiuri
cilebis mier epiTeliocitTa momwifebis da apoptozis procesebis
normaluri mimdinareobis darRvevisa.
miuxedavad daavadebis mkurnalobaSi danergili axali meTodebisa,
dReisaTvis fsoriazis Terapia kvlav aqtualuria, radgan
