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.