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1、自制肝保护液对梗阻性黄疸大鼠门静脉阻断所致肝细胞损伤的保护作用冯春林1,2,林恒1,陈炜2,冷凯2,郑晓华2,主鹤亭2,别平1(400038重庆,第三军医大学西南医院肝胆外科研究所1;563000贵州遵义,遵义医学院第三附属医院肝胆外科2)[摘要]目的探讨自制肝保护液对梗阻性黄疸大鼠门静脉阻断所致肝细胞损伤的作用及对肝细胞MAPKs信号途径的影响。方法72只Wistar系大鼠完全随机分为4组:A组:胆道再通、门静脉周围游离、切除肝尾状叶,90min后关腹腔;B组:胆道再通、肝尾状叶分流门静脉、余肝门静脉血流阻断90min、恢复
2、正常门静脉血流、切除肝尾状叶,关腹;C组:B组+门静脉肝侧灌注4℃乳酸林格氏液;D组:B组+门静脉肝侧灌注4℃自制肝保护液(home-madeliversolution,HMLS)。术后0、6、24h获取各组大鼠组织标本。采用RT-PCR和Westernblot分别测定肝组织A20mRNA和蛋白表达,测定肝组织中p-JNK、p-ERK、p-p38、Bcl-2、Bax和Caspase-3的蛋白表达情况,TUNEL法检测肝细胞凋亡指数。结果D组大鼠A20mRNA和蛋白表达均明显增加(P<0.05),p-JNK、Bax、Caspas
3、e-3蛋白表达明显下降(P<0.05),而p-ERK、Bcl-2蛋白表达明显增加(P<0.05)。C、D组大鼠与B组相比肝细胞凋亡率明显下降(P<0.05),其中D组下降更明显。结论自制肝保护液经门静脉在体持续低温灌注肝脏,可以促进A20mRNA及其蛋白的高表达,由此激活ERK信号转导通路,抑制JNK信号转导通路,反向调节线粒体途径Bcl-2/Bax蛋白平衡的逆转,降低了其下游的凋亡执行蛋白Caspase-3,从而起到抗凋亡、保护肝细胞的作用。[关键词]梗阻性黄疸;门静脉血流阻断;自制肝保护液;MAPK信号转录途径[中图法分类
4、号][文献标志码]AEffectofhomeself-madeliversolutiononMRPKsignaltranscriptionalpathwayinobstructivejaundiceratsafterportalveinocclusioninratswithobstructivejaundiceFengChunlin1,2,LinHeng1,ChenWei2,LengKai2,ZhengXiaohua2,ZhuHeting2,BiePing1(InstituteofHepatobiliarySurgery,So
5、uthwestHospital,ThirdMilitaryMedicalUniversity,Chongqing,400038;DepartmentofHepatobiliarySurgery,ThirdAffiliatedHospitalofZunyiMedicalCollege,Guizhou,ZunyiProvince,563000,China)FengChunlin1,2,LinHeng1,ChenWei2,LengKai2,ZhengXiaohua2,ZhuHeting2,BiePing1(InstituteofHe
6、patobiliarySurgery,SouthwestHospital,ThirdMilitaryMedicalUniversity,Chongqing,400038;DepartmentofHepatobiliarySurgery,ZunyiHospital,Zunyi,GuizhouProvince,563000,China)[Abstract]ObjectiveToexploretheeffectofhomeself-madeliversolutiononMRPKsignaltranscriptionalpathway
7、afterportalveinocclusioninratswithobstructivejaundice.Methods72Seventy-twoWisitarratswererandomlydividedintofourgroups:,groupA(biliarytractrecanalization,liberationofportalvein,resectionofcaudatelobeofliverandclosureofabdomenatin90min),groupB(biliarytractrecanalizat
8、ion,portalveinbypassincaudatelobeofliver,PVOoflefthepatictissuein90min,thenrecoveryofportalveinflowandresectionofcaudatelobeofliver),group