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ID:28129358
大小:13.38 MB
页数:125页
时间:2018-12-08
《like receptor 24二聚体介导了小鼠脑出血炎症损伤》由会员上传分享,免费在线阅读,更多相关内容在应用文档-天天文库。
1、第三军医大学博士学位论文TUNELTerminal—deoxynucleoitidyITransferase原位末端标记法MediatedNickEndLabelingWBWesternblot免疫蛋白质印迹WTWildtype野生型2万方数据第三军医大学博士学位论文Toll·likereceptor2/4heterodimermediatesinflammatoryinjuryinintracerebralhemorrhage士AbstractIntracerebralhemorrhage(ICH)representsth
2、eacutemanifestationofprogressivecerebralsmall—vesseldisease.ICHisassociatedwithhighrateofmortalityandmorbidity.Itaccountsforabout10%to15%ofallstrokesworldwide.Currently.thereisnoeffectivetherapytoimprovesurvivalrateortreatmenttoimprovethequalityoflifeforsurvivors.I
3、CHismainlycausedbymechanicalinjurythatresultsincompressionbecauseofthemasseffectofhematoma.Buttheclinicaltrialsforsurgicalhematomaevacuationhadanunfavourableoutcomeversusconservativetreatment.IncreasingevidenceindicatesthatsecondaryinjuryfollowingICHplaysallimporta
4、ntroleintheneurologicaldeteriorationexperiencedbypatientswithICH.ThesecondarybraininjuryafterICHisincludinghematomatoxicity,highmetabolicinjury,excitotoxicity,oxidativestress,andinflammatoryinjury.Innateimmunityandinflammatoryresponseshavebeenfoundtoplaycriticalrol
5、esinICH-inducedsecondarybraininjury.Toll—likereceptors(TLRs)thatrecognizedistinctpathogen-associatedanddamage-associatedmolecularpatternsplayakeyroleininnateimmunityandinflammatoryresponses.RecentlystudiessuggestedthatTLR4maybetheupstreamsignalthattriggersinflammat
6、oryinjuryinICH.OurpreviouSstudysuggestedthatHbpotentiatesmicroglialactivationviaTLR4,inturninducingNF-kappaBactivationviatheMyD88/TRIFsignalingpathway,andultimatelyincreasingcytokineexpressionandinflammatoryinjuryafterICH.However,theinflammationinjurywasnotcomplete
7、lyinhibitedwhenTLR4signalingwasblockedTherecentidentificationofCO—receptorsthatenhanceTLRsfunctionsuggestsanemergingparadigminwhichTLRsacttogetherwithothercellsurfacemoleculestobridgemicroberecognitionandinitiationofsignalingresponses,forexample,NationalNaturalScie
8、nceFoundationofChinar81400974),NationalBasicResearchProgramofChina(973Program,2014CB541605)万方数据TLRl/TLR2andTLR2/TLR6heterodimersinischemicbrainin
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