plaferoni lb-s da diazepamis zegavlena eqsperimentuli cxovelebis ujredebSi genebis eqspresiaze halotaniT narkozis dros
d. mxiTariani, g. kapanaZe, l.ZiZiguri, m.giorgobiani,
z.vadaWkoria, d. ZiZiguri
iv.javaxiSvilis sax. Tbilisis sax. universiteti, citologiis,
histologiis da ganviTarebis biologiis kaTedra,
Tbilisis sax. samedicino universitetis bavSvTa qirurgiis anesTeziologiis da reanimaciis kaTedra,
bavSvTa asakis stomatologiis kaTedra, saxisa da ybebis ganviTarebis Tandayolili
mankebis mqone bavSvebis dispanserizaciis, mkurnalobis da reabilitaciis
respublikuri centri
cnobilia,
rom operacia da narkozi iwvevs imunosupresias, romlis xarisxi ganapirobebs
garTulebebs postoperaciul periodSi(8). gansakuTrebiT sayuradReboa inhalaciuri
anesTetikis halotanis imunosupresiuli efeqti, vinaidan is farTod gamoiyeneba
bavSvTa zogad qirurgiasa da yba_saxis qirurgiaSi(9). postoperaciuli periodis
xangrZlivoba da misi mimdinareoba garTulebis gareSe damokidebulia imunuri
sistemis stabilur mdgomareobaze, risTvisac mowodebulia pre-, intra da
postoperaciuli imunostimulaciisaTvis sxvadasxva meTodebi da
medikamentebi(10).
dadgenilia,
rom daaxloebiT yoveli xuTasi bavSvidan
erTi ibadeba yba-saxis paTologiiT. bolo dros am darRvevebis mkurnalobaSi
SeimCneva progresi. kerZod, adreul asakSi Catarebuli operaciis Sedegad pacientebi agrZeleben srulfasovan
cxovrebas(5). saqarTveloSi zeda tuCisa da sasis Tandayolili napralis
gavrcelebis maCvenebeli 1980-90wlebSi Seadgens 1,19(anu napralis mqone erTi
bavSvi:840 cocxladSobilze) (11).
cnobilia, rom aRniSnuli paTologiis mqone bavSvebs axasiaTebT sxvadasxva
organoTa sistemebis upiratesad sasunTqi, gul-sisxlZarRvTa da imunuri sistemebis
mxriv cvlilebebi(11). aRniSnuli Tandayolili paTologiebis rekonstruqciuli
operaciebis SemTxvevaSi anesTeziis erT-erTi meTodia endotraqealuri narkozi.
gamomdinare
iqidan, rom operacia da narkozi TavisTavad warmoadgens posthipoqsiuri da
imunosupresiuli cvlilebebis ganviTarebis safrTxes, aucilebelia aRniSnuli
kontingentis bavSvebisTvis anesTeziis optimaluri pirobebis SerCeva. am
TvalsazrisiT didi mniSvneloba eniWeba srulyofil premedikacias.
Pliteraturuli
monacemebis Tanaxmad, yba-saxis paTologiis SemTxvevaSi xSirad gamoiyeneba
premedikaciaSi sedaciuri preparatebi. ufro xSirad am mizniT iyeneben midazolams,
romelsac aqvs upiratesoba acetaminofenTan da sxva anesTeziuri preparatebTan
SedarebiT(4). garda amisa, aRniSnuli paTologiis bavSvebSi dadebiTi Sedegebi
aqvs diazepamis gamoyenebas (7).
gamomdinare iqidan, rom zeda tuCisa da sasis Tandayolili napralis mqone
bavSvebSi aRiniSneba imunuri depresia(11), sedaciur preparatebiT
premedikaciasTan erTad mizanSewonilad miviCnieT imunomodulatorebis gamoyeneba.
upirveles yovlisa saWiro iyo am mizniT gamoyenebuli farmakologiuri preparatebis
ujredebis funqciur aqtiurobaze zegavlenis
Seswavla. gansakuTrebiT sainteresod miviCnieT maTi genetikuri aparatis
saregulacio meqanizmebze zemoqmedebis dadgena.
zemoT Tqmulidan gamomdinare miznad davisaxeT
Segveswavla eqsperimentuli cxovelebis filtvis da RviZlis qsovilebis ujredebSi
genebis eqspresiaze plaferoni lb-s(imunomodulatoriT prevencia) da
diazepamis(premedikacia) zegavlena halotaniT narkozis dros.
masala da meTodebi. kvlevis
obieqtad gamoyenebuli iyo 30 TeTri zrdasruli virTagva(123-140g.).
imunomodulatoris saxiT gamoviyeneT samamulo preparati - plaferoni lb, romelic
SemuSavebulia saqarTvelos mecnierebaTa akademiis samedicino bioteqnologiis
institutSi. plaferoni lb-s farmakologiur efeqtebidan CvenTvis saintereso iyo
misi imunomamodulirebeli moqmedeba. premedikaciisTvis SevarCieT preparati
diazepami, romelic iwvevs postoperaciuli hipoqsiis Semcirebas. narkozisTvis
gamoviyeneT halotani. eqsperimentuli
cxovelebi davyaviT xuT jgufad. 1 - sakontrolo jgufi; 2-intaqturi cxovelebi,
romelTac halotaniT narkozis Semdeg gaukeTdaT cru operacia; me-3 jgufis
virTagvebs anesTeziamde 30 wuTiT adre SevuyvaneT diazepami(0,2mg\kg) + halotani
da cru operacia; me-4 da me-5 jgufebis eqsperimentul cxovelebSi Segvyavda
plaferoni lb(14g\140g)
erTi kviris ganmavlobaSi. erTi kviris Semdeg me-4 jgufis cxovelebs halotaniT
anesTeziis Semdeg CautardaT cru operacia, me-5 jgufis cxovelebSi operaciamde 30
wuTiT adre gavukeTeT diazepami +
halotaniT narkozi da cru operacia.
filtvis da RviZlis qsovilebidan birTvebis
izolirebas vaxdendiT Sovos meTodiT (1). birTvebSi dezoqsiribonukleinis mJavas
raodenobas vsazRvravdiT sadovskisa da sternis (6) mixedviT. filtvis da RviZlis
ujredebis birTvebis transkripciul aqtiurobaze vmsjelobdiT mJavaSi uxsnad
fraqciaSi 14C-utf-is CarTvis intensiurobis
cvlilebis mixedviT(2).
Sedegebi.
SeviswavleT halotaniT narkozis zemoqmedeba TeTri virTagvas filtvis da RviZlis
ujredebis birTvebis transkripciul aqtiurobaze. aRmoCnda, rom halotani
ainhibirebs transkripciis process mxolod filtvis qsovilebis ujredebis birTvebSi. 14C-utf-is
CarTvis intensiuroba 22%-iT qveiTdeba sakontrolo maCveneblTan SedarebiT(sur.1).
narkoziT ganpirobebuli inhibirebis efeqti ixsneba diazepamiT premedikaciis
Semdeg. kerZod, preparatis moqmedebis Sedegad(premedikacia) eqsperimentul
virTagvebis filtvis ujredebis birTvebSi genebis eqspresia daaxloebiT 30%-iT
izrdeba pirveli jgufis cxovelebTan SedarebiT, xolo me-2 jgufis Sesabamis
maCvenebels 50% aRemateba(sur.1).
analogiuri
efeqti miRebuli iyo plaferoniT prevenciis Semdegac. plaferonis ineqciebi erTi kviris ganmalobaSi aseve xsnis rnm-s
sinTezze halotanis damTrgunvel zemoqmedebas filtvis qsovilis ujredebSi(sur.1).
aRsaniSnavia, rom plaferoni lb-iT prevenciis fonze cxovelebSi diazepamiT premedikacia (0.5 sT. operaciamde) filtvis
ujredebSi birTvebis transkripciuli aqtiurobis daqveiTebas ganapirobebs.
filtvis ujredebisagan gansxvavebiT TeTri
virTagvas RviZlis ujredebis birTvebis transkripciuli aqtiuroba ucvleli rCeba
halotaniT narkozis Semdeg(sur. 2). amave dros hepatocitebis birTvebis
transkripciuli aqtiuroba sakontrolo jgufTan SedarebiT 14%-iT izrdeba diazepamiT
premedikaciis Semdeg. sainteresoa hepatocitebis birTvebSi rnm-s sinTezis
plaferoniT ganpirobebuli aqtivacia. kerZod, plaferonis ineqciebi erTi kviris
ganmalobaSi daaxloebiT 70%-iT zrdis izolirebuli birTvebis rnm-masinTezirebel
aqtiurobas. aRsaniSnavia, rom iseve rogorc filtvis ujredebis birTvebSi,
plaferoni lb-iT prevenciis fonze
diazepamis premedikacia (0.5 sT. operaciamde) RviZlis ujredebSic
birTvebis transkripciuli aqtiurobis daqveiTebas ganapirobebs(sur.2).
gansja. yba-saxis qirurgiaSi narkozis da operaciis
garTulebebis Tavidan acilebis mizniT atareben premedikacias sedaciuri
preparatebiT. naCvenebia, rom diazepamis antihipoqsiuri Tvisebidan gamomdinare
zeda tuCisa da sasis napralis mqone
bavSvTa kontigentSi ar vlindeba zemoT aRniSnuli garTulebebi(7).
aranakleb mniSvnelovania aRniSnuli paTologiebis bavSvebSi
zomierad gamoxatuli imunosupresiiT ganpirobebuli postoperaciuli garTulebebi.
cnobilia,
rom eqsperimentul cxovelebze Catarebuli mravalricxovani gamokvlevebi saSualebas
iZleva gacilebiT meti sizustiT davadginoT sxvadasxva farmakologiuri
preparatebis zemoqmedebiT ganpirobebuli cvlilebebi ujredul da subujredul
doneebze. amave dros dadgenilia, rom calkeuli ujredebis iseve rogorc mTliani
organizmis formirebisa da normaluri funqcionirebisaTvis aucilebel pirobas
warmoadgens genebis eqspresiis regulacia. zemoT Tqmulidan gamomdinare
SeviswavleT TeTri virTagvas filtvis da RviZlis qsovilebis ujredebSi genebis
pirvelad aqtiurobaze(transkripciis procesze) plaferoni lb-s da sedatiuri
premedikaciuli preparatis, diazepamis
zegavlena halotaniT narkozis
dros.
gamokvlevebiT
dadginda, rom anesTeziis mizniT halotanis gamoyeneba iwvevs transkripciis
procesis inaqtivacias mxolod filtvis qsovilis ujredebSi. rnm-s sinTezis narkoziT
ganpirobebuli inhibirebis efeqti ixsneba diazepamiT premedikaciis SemTxvevaSi.
miRebuli Sedegebi kargad korelirebs klinikuri gamokvlevebis monacemebTan,
romelTa Tanaxmadac diazepamis gamoyenebis SemTxvevaSi yba-saxis paTologiebis
mqone bavSvebSi ar aRiniSneba postoperaciuli garTulebebi(7).
literaturuli monacemebiT, virTagvas RviZlis ujredebze plaferonis mastimulirebeli zemoqmedeba satranskripcio aparatis doneze xorcieldeba(3). plaferonis mastimulirebeli zemoqmedeba dadgenili iqna Cvens mier virTagvas filtvis da RviZlis ujredebis birTvebze preparatis erTi kviris ganmavlobaSi yoveldRiuri ineqciebis Sedegad. aRsaniSnavia, rom plaferoni lb-s da diazepamis erTdrouli gamoyenebis SemTxvevaSi orive qsovilis ujredebSi rnm-s sinTezis mniSvnelovani inhibireba xdeba. miRebuli Sedegebidan gamomdinareobs, rom rogorc diazepami, aseve plaferoni lb(cal-calke) ujredebis funqciuri aqtiurobis gazrdas ganapirobebs. maTi erTdrouli ineqciebiT ganpirobebuli inhibirebis efeqti SeiZleba aixsnas preparatebis SeuTavseblobiT, rac damoukidebli kvlevis sagans warmoadgens da klinikaSi maTi gamoyenebis SemTxvevaSi unda iyos gaTvaliswinebuli.
literatura: M
1. Chauveau T., et
al. Isolation of
pure and unaltered
liver nuclei; Morphology
and
Biochemical composition. Exs
Cell Res, 1956
V/11 , pp317-321.
2.KD.V
Dzidziguri, P. V. Chelidze, M. A. Zarandia, E. C. Cherkezia and
G. D. Tumanishvili
Transcriptional Activiti and
Ultrastructure of Morphologically Different
Types of Nucleoli Isolated
from Hepatocytes of
Normal and Hepatectomized Rats Epit.Cell Biol
(1994) 3: 54-60 1994
Sringer-Verlag London Limited
3. Gagua
M.., Dzidziguri D.., Mikadze E., Bakhutashvili V. Study of Plaferon LB influece
on white rat hepatocytes morfo-functional
activity.Bull. of the Academ. of Sci. of Georgia, 1999, 2:56-58.
4. Kain ZN, Mayes LC, Wang SM., Hofstadter MB.
Postoperative behavioral outcomes in chidren: effects of sedative
premedication. Anaesthesiology 1999 Mar 90:758-65.
5. Kang MY, Tsuchiya M, Packer L, Manabe M. In vitro study on antioxidant potential of various drugs used in the preoperative period. Acta Anaesthesiol Scand 1998 Jan 42:4-12
6. Sadovski P.P., Stern
J. W. Cell Biol.
1968 V.37 pg 147-164.
7.Vadachkoria Z., Giorgobiani M., Dzidziguri L., Some
Peculiarities of Anesthesia at the Lip and Palate Plastics. in press.
8.m.giorgobiani, r.kutubiZe. ftorotaniT
narkozis gavlena imunur statusze bavSvebSi. Tssu SromaTa krebuli. Tbilisi,
1996, 32, 76:77.
9.Ì.Ãðèãàëàøâèëè Ç.Âàäà÷êîðèÿ
Ì.Ãèîðãîáèàíè Ïðîôèëàêòèêà
ïîñòîïåðàöèîííîé äåïðåñèè êëåòî÷íîãî è ãóìîðàëüíîãî èììóíèòåòà ïðè
óðàíîïëàñòèêå Ñáîðíèê íàó÷íûõ òðóäîâ
ÒÃÌÓ 1996ã 32,117;120
10. Á. Êîðñàíòèÿ
Ñ. Êóðàäçå è äð. Îïûò ïðèìåíåíèÿ
ëèíãâàëüíîé ôîðìû ïëàôåðîíà ïðè îñòðûõ õèðóðãè÷åñêèõ èíôåêöèÿõ. International Journal on
Immunorehabilitation.
11.z.vadaWkoria. saxis Tandayolili napralis
mqone bavSvTa samedicino reabilitaciis ZiriTadi aspeqtebi. avtoreferati. 1996.
Summery
The influence of prevention by immunomodulator and sedative
premedication on the genes expression in cells of lung and liver tissues of
experimental animals (white rat) at inhalative anesthesia with halotane was
studied. It was established that inhalative anesthesia via halotane inhibits
the process of transcription only in nuclei of lung cells. The inhibition
effect stipulated by anesthesia is removed after premedication with diazepam.
The analogous effect was observed also after prevention via plaferone. At thf
same time the inhibition of RNA- synthesis takes place in cells of both tissues
by simultaneous application of abovementioned drugs.