like receptor 24二聚体介导了小鼠脑出血炎症损伤

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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