mtor信号通路在大鼠脑缺血-再灌注损伤中的作用

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1、万方数据英文摘要EffectofmTORsignalingpathwayonischemia—reperfusioninjuryinratsColledgeofPharmaceuticalScience，ZhejiangUniversityPharmacyCandidateforMasterSupervisorAbstractHuadanZhangProf．LinghuiZengobjective：CerebralischemiaiSaseriousdiseasewhichlcadstoextensivecerebraldamageandseriousneurologic

2、aldeficits．Tillnow，tissueplasminogenactivator(tPA)remainstheonlyapproveddrugproventOimproveclinicaloutcomew翊、ischemicstroke．However．theuseoftPAiSlimitedbecauseofanincreasedriskofhemorrhagefewhourspost—stroke．Therefore，itisurgentforinvestigatingnewtherapeuticstrategiesforisehemicstroke。Mam

3、maliantargetofraparnycin(roTOR)isacriticalregulatorofcellgrowthandmetabolismthatisimplicatedinmanydiseases．Rapamycin，aninhibitorofmTOl乙wasdiscoveredtoantagonizetheanti—apoptoticsignalsandstimulateautophagytomaintainnormalcellmetabolism．Ithasalsodemonstratedeffectsinbehavioralandlearningin

4、theanimalmodeloftraumaticbraininjury．However,theeffectandmechanismofmTOR—mediatedprotectioninischemicstrokeisunclear．Inthepresentstudy，weexploredwhetherthemTORsignalingpathwayisinvolvedinischemia-reperfusioninjuryinSDrats．Methods：wecarriedoutmiddlecerebralarteryocclusion(MCAO)withsutureme

5、thodinSDratstomimictheprocessofhumancerebralischemia．neneurologicalcriterionofratsatdifferenttimepointsafterMCAOmodelingWasmonitored．ThechangesofthemTORsignalingpathwayindifferenttimepointandbrainareaweredetectedusingWesternBlotafterMCAOmodeling．TTCstainingwasusedtoanalyzetheinfarctsizebe

6、foreandaftermodeling．FJBstainingWascarriedouttomeasureapoptoticcells．CD68fluorescentstainingWasusedtomeasurethenumberofmicroglialcell．Results：mTORpathwaywasactivatedTV万方数据浙江大学硕士学位论文英文摘要60minutesafterMCAOintheischemicpenumbra．Aswesetischemictimefor1handobservedmTORpathwayatdifferentinterva

7、lsofreperfusion，wefoundthatactivationofmTORpathwaykeptathigherlevelfrom6hhoursafterperfusion．Long-termmonitoringafterischemiashowedthatmTORsignalingpathwaystillkeptathighlevelfrom2weeks．Pre·administrationandpost—administrationofrapamycinsignificantlyimprovedneurolog