肝细胞核因子3β调控小鼠体内HBV转录和复制的实验研究  

Hepatocyte nuclear factor 3β regulates hepatitis B virus transcription and replication in HBV replication model mice

作　　者：韩红霞[1] 刘凤君[1] 侯全玲[2] 王月宾[1] 尹华[1] 崔尧丽[1] 唐红[1] 

机构地区：[1]四川大学华西医院感染性疾病中心,生物治疗国家重点实验室[四川大学]感染性疾病分子生物学研究室四川大学华西医院感染性疾病中心,生物治疗国家重点实验室感染性疾病分子生物学研究室,四川成都610041 [2]四川大学基础医学院与法医学院法医病理教研室,四川成都610041

出　　处：《四川医学》2008年第5期495-497,共3页Sichuan Medical Journal

基　　金：国家重点基础研究规划(973计划)项目(2006CB504300和2007CB12900)资助

摘　　要：目的应用复制型HBV小鼠模型观察肝细胞核因子3β(HNF3β)对小鼠体内HBV转录和复制的调控作用。方法通过尾静脉高压注射法将复制型HBV重组质粒pHBV4.1和大鼠HNF3β表达质粒pCMVHNF3β导入小鼠体内,用Northern吸印杂交检测小鼠肝组织中HBV3.5kb、2.4/2.1kb、0.7kb mRNA的转录情况,Southern吸印杂交检测HBV DNA复制中间体水平。结果经小鼠尾静脉高压注射法体内转染质粒pHBV4.1后,小鼠肝组织中检测到HBV3.5kb、2.4/2.1kb mRNA转录信号和HBV DNA复制中间体信号;与共转染pHBV4.1和空载质粒pCMVpA对照组相比,共转染pHBV4.1和pCMVHNF3β使HNF3β过量表达,明显降低了小鼠体内HBV RNA转录和DNA复制水平。结论肝富集转录因子HNF3β对小鼠体内HBV转录和复制具有抑制作用,有可能成为今后抗HBV生物治疗新的靶点。Objective To investigate the effects of hepatocyte nuclear factor 3β（HNF3β） in regulating HBV transcription and replication in vivo,using a mouse model with hepatitis B virus（HBV） replication. Methods The replication-competent HBV recombi- nant plasmid pHBV 4.1 plus rat HNF3β expression plasmid pCMVHNF3β were eotranfected into BALB/c mice via the tail vein, using a hydrodynamics-based in vivo transfection procedure. The transcription levels of 3.5kb, 2.4/2.1 kb and 0.7kb HBV RNA in the mice liver were analyzed by Northern blot hybridization, and the level of HBV DNA replication intermediates was detected by Southern blot hybridization analysis. Results After hydrodynamic in vivo transfection, HBV3.5kb.2.4/2. lkb mRNA and HBV DNA replication intermediates were detected in the mice liver. Increased expression of HNF3β in the HBV replicative mice by cotransfection with pCMVHNF3β reduced viral transcription and replication,by comparing with those cotransfected with the empty control plasmid pCMVpA. Conclusion Liver-enriched transcription factor HNF3β could inhibit HBV transcription and replication in vivo, which may represent a potential target for antiviral biotherapy for HBV infection in future.

关 键 词：肝细胞核因子3β 乙型肝炎病毒 转录 复制 

分 类 号：R346[医药卫生—基础医学]