异氟醚预处理对大鼠局灶性脑缺血再灌注时TLR4和MyD88表达的影响肖志彬高昌俊唐晓旭张振王君张玉明柴伟孙绪德基金项目：国家自然科学基金（30972833）作者单位：710038西安市，第四军医大学唐都医院麻醉科（肖志彬、高昌俊、张振、王君、张玉明、柴伟、孙绪德）；北京后勤指挥学院门诊部（唐晓旭）通信作者：孙绪德，Email：sunxude@fmmu.edu目的评价异氟醚预处理对大鼠局灶性脑缺血再灌注时Toll样受体4（TLR4）和Myd88表达的影响。方法雄性成年SD大鼠54只，体重250～300g，随机分为3组（n=18）：假手术组（S组）仅分离血管，不留置线栓；脑缺血再灌注组（IR组），采用线栓法制备大鼠局灶性脑缺血再灌注模型，缺血2h，再灌注24h；异氟醚预处理（IP组）吸入2%异氟醚，1h/d，连续5d，处理结束24h时制备大鼠局灶性脑缺血再灌注模型。再灌注24h时进行神经功能缺陷评分，然后每组处死3只大鼠，测定脑梗死体积。分别于再灌注24、48和72h时，处死5只大鼠，取脑组织，采用Westernblot法测定TLR4、髓样分化因子88（MyD88）及NF-κB的表达水平。结果与S组比较，IR组和IP组神经功能缺陷评分升高，脑梗死体积增大，TLR4、MyD88和NF-κB的表达均上调（P＜0.05）；与IR组比较，IP组神经功能缺陷评分降低，脑梗死体积减小，TLR4、MyD88和NF-κB的表达均下调（P＜0.05）。结论异氟烷预处理可通过抑制TLR4-MyD88信号通路，减轻炎性反应，从而减轻大鼠局灶性脑缺血再灌注损伤。【关键词】异氟醚；缺血预处理；Toll样受体4；髓样分化因子88；再灌注损伤；脑Isofluranepreconditioningprotectsratbrainsagainstfocalischemiabytoll-likereceptor4myeloiddifferentiationfactor88-dependentsignalpathwayXIAOZhi-bin*,GAOChang-jun,TANGXiao-xu,ZHANGZhen,WANGJun,ZAHNGYu-ming,CHAIwei,SUNXun-de.*DepartmentofAnesthesiology，TangduHospital，FourthMilitaryMedicalUniversity，Xi′an710032，China---本文来源于网络，仅供参考，勿照抄，如有侵权请联系删除---Correspondingauthor:SUNXun-de,Email:sunxude@fmmu.eduABSTRACT:ObjectiveToexploretheprotectivefunctionoftoll-likereceptor4myeloiddifferentiationfactor88-dependentsignalpathwayinIsofluranepreconditioningprotectsratbrainsagainstcerebralischemia/reperfusion.Methods54MaleSprague-Dawley(SD)ratsweighing250~300gwererandomlydividedintothreegroup:controlgroup(don'tinsertnylonthreadintorightInternalcarotidartery,juststripvessel,n=18),Mcaogroup(threadembolismwasperformedtoestablishmiddlecerebralarteryischemia/reperfusionmodeln=18),Isofluranepreconditioninggroup(Isogroup)(inhalationof2%isofluraneand98%O21hperdaylasting5d,n=18),After24hunderisofluranepreconditioningrightMCAOwasinducedbyanylonthreadinsertedcraniallyintorightinternalcarotidartery.Scoresofneurologicimpairmentandcerebralinfarctvolumeweremeasuredafterischemiafor2hoursandreperfusionfor24hours.WesternblotwereusedtoanalysetheexpressionofTLR4,Myd88,andNF-κBproteinlevelondifferenttimepointsinischemicbraintissue.ResultsComparedwithMcaogroup,Isogroupmicepresentedasignificantdeclineintheneurologicimpairmentscoreat24hfollowingreperfusion,Meanwhile,cerebralinfarctvolumeofIsogroupmiceweredecreased(p＜0.05).theproteinlevelsofTLR4inIsogroupwasobviouslylowerthanthoseinMcaogroup.AndtheproteinlevelsofTLR4reachingthemaximumat24h,thereaftergraduallydecreased48~72h(p＜0.05).theexpressionofMyd88andNF-κBproteininIsogroupwasdecreasedandreachedthepeakat24hafterreperfusioninthecerebralcortexoftheischemic(p＜0.05).ConclusionsIsopreconditioningprotectedthebrainfromdamagemaybeinvolvedinthemechanismofthrougdownregulationofTLR4,Myd88,andNF-κB.Isoflurane;Ischemicpreconditioning;Toll-likereceptor4;Myeloiddifferentiationfactor88；Reperfusion...