n乙酰半胱氨酸对小鼠缺血再灌注损伤肝肺组织中toll样受体表达的影响及保护作用-effect and protective effect of n - acetylcysteine on toll - like receptor expression in liver and lung tissue of mice with ischemia-reperfusion injury.docx

英文缩略词缩略语TLR英文全称Tolllikereceptor中文全称Toll样受体PRRsPAMPpatternrecognitionreceptorsPathogenassociatedmolecularpattern模式识别受体病原相关分子模式I/RROSSIRSALINACGSHTNF-αIschemia-reperfusionReactiveoxygenspeciesSystemicinflammatoryresponsesyndromeAcutelunginjuryN-acetylcysteinereducedglutathionehormoneTumornecrosisfactor-α缺血再灌注活性氧全身炎症反应综合征急性肺损伤N-乙酰半胱氨酸还原型谷胱甘肽肿瘤坏死因子-αALTILW/DNF-κBAPCsRT-PCRELISAalaninetransaminaseInterleukinWet/dryratioNucleartranscriptionFactor-kappaBAntigenpresentingcellsReal-timePCREnzymelinkedimmunosorbentassay丙氨酸转氨酶白介素湿干重量比核转录因子-κB抗原提呈细胞实时定量PCR酶联免疫吸附实验N-乙酰半胱氨酸对小鼠缺血再灌注损伤肝肺组织中Toll样受体表达的影响及保护作用华中科技大学同济医学院附属协和医院胰腺外科中心硕士研究生：金鑫导师：吴河水教授中文摘要目的研究抗氧化剂N-乙酰半胱氨酸（NAC）对小鼠肝脏缺血再灌注损伤模型肝和肺组织中Toll样受体2（TLR2）和Toll样受体4（TLR4）表达的影响及保护作用。方法以BALB/C小鼠复制肝脏部分缺血再灌注损伤模型，将小鼠随机分为3组：假手术对照组（SH组），缺血再灌注组（I/R组）和NAC实验组（I/R-NAC组）。分别于再灌注后1小时、3小时取静脉血测定血清TNF-α浓度和ALT水平；取肺组织标本测湿干重量比及送病理切片；同时取受损肝、肺组织行RT-PCR和Westernblot以观测TLR2/4表达的变化。结果1.肺组织病理结果显示I/R组肺组织毛细血管充血，肺泡结构破坏，肺泡间质粒细胞浸润，肺泡腔内不同程度渗出及少量红细胞。肺湿干重量比显示肺水肿(P0.05)。2.缺血再灌注后受损肝叶和肺组织内均出现TLR2/4mRNA和蛋白水平的高表达(P0.01)。3.缺血再灌注后静脉血清TNF-α浓度和ALT水平较假手术组显著升高(P0.01)。4.NAC干预后，肺水肿明显减轻；TLR2/4mRNA和蛋白表达受到抑制(P0.05)；血清TNF-α浓度和ALT水平较I/R组明显下降(P0.05)。结论小鼠肝部分缺血再灌注后，TLR2/4不仅在受损肝组织内有表达，在远端器官肺组织内也有表达。N-乙酰半胱氨酸可通过调整氧化还原状态，抑制再灌注后TLR2/4的活化和细胞因子TNF-α的表达，从而减轻肝、肺组织的损伤。关键词N-乙酰半胱氨酸、缺血再灌注、肺损伤、Toll样受体InfluenceofN-acetylcysteineontolllikereceptoranditsprotectiveeffectonliverandlunginmiceafterischemia-reperfusioninjuryCenterofPancreaticSurgery，UnionHospital，TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnologyMastercandidate:JinXinTutor:Prof.WuHe-shuiAbstractObjective:ToinvestigatetheinfluenceofNAConTLR2/4geneexpressionandtheprotectiveeffectofNAConliverandlunginmiceafterhepaticischemia/reperfusioninjury.Methods:BALB/cmicewereusedinamodelofpartialhepaticI/Rinjuryandrandomlysubjectedtosham-operatedcontrolgroup(SH),hepaticischemia/reperfusiongroup(I/R)orNACpretreatedinhepaticI/Rgroup(I/R-NAC).ThelevelofTNF-αinportalveinandplasmaALTweremeasuredat1hourand3hourrespectivelyafterreperfusion.Lungtissuewet-