shh信号通路对大鼠脑缺血后的保护作用与机制

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1、上海交通大学硕士学位论文的表达促进血管新生，增加MCAO模型大鼠血流灌注和血管新生，减少脑梗死体积，改善神经功能评分。本研究为认识SHH信号通路在急性脑梗死大鼠血管新生中的作用提供了实验基础。关键词：VEGF；Ang-1；SonicHedgehog(SHH)信号通路；血管新生；血管性血友病因子-II-上海交通大学硕士学位论文EFFECTSOFTHESONICHEDGEHOGSIGNALINGPATHWAYONNEOVASCULARIZATIONINRATSWITHCEREBRALISCHEMIAABSTRACTObjective:Toexploretheeffectoftheacti

2、vatedsonichedgehogsignaling(SHH)pathwayonneovascularizationinratswithcerebralischemia.Methods:Themodelofmiddlecerebralarteryocclusion(MCAO)inratswasinducedbynylonsutureembolisation.Alltheratswererandomlydividedintofourgroups:Shamoperationgroup,MCAO+PBSgroup,MCAO+SHH(SHHsignalingpathwayagonist)g

3、roup,andMCAO+SHH+CYC(SHHsignalingpathwayantagonist)group.Threedaysorsevendayslater,theneurologicaldeficitswereassessedbyLongastandard,theinfarctvolumewereacquiredusingtheAISimagingresearchsoftware,thecerebralbloodflow(CBF)weremeasuredwithlaserDopplerflowmeter,thetotalbloodvessellengthonthesurfa

4、ceofleftbrainhemispherewasconductedbyusingAISimagingresearchsoftware,thelevelsofvWFweremeasuredbyimmunohistochemistry.Theexpressionsofneovascularizationfactors(VEGFandAng-1)weredetectedbyRT-PCRandwesternblot.Results:ComparedwithMCAO+PBSgrouponday3andday7,thelevelofneurologicaldeficitsandinfarct

5、volumeinMCAO+SHHgroupwereobviouslydecreased,thelevelofCBF,totalbloodvessellengthand-III-上海交通大学硕士学位论文expressionofvWF,VEGFandAng-1weresignificantlyincreased.AfterblockedwithCYC,thelevelofneurologicaldeficitsandinfarctvolumewereobviouslyincreased,thelevelofCBF,totalbloodvessellengthandexpressionof

6、vWF,VEGFandAng-1weredecreasedsignificantly.Conclusion:ActivationofSHHpathwaycanimproveneurologicalfunctionalrecovery,increasethecerebralbloodflowandpromoteneovasculationafterMCAO.VEGFandAng-1maybethedownstreammoleculesofSHHpathwayandplayakeyroleinneovasculation.Ourresultssuggestapotentialroleof

7、SHHsignalingpathwayinneovascularizationafterstroke.KEYWORDS:VEGF；Ang-1；SonicHedgehog(SHH)signalingpathway；neovascularization；vWF-IV-上海交通大学硕士学位论文目录第一章绪论...............................................................................