恩替卡韦抑制乙型肝炎病毒复制型小鼠体内病毒的复制  

Entecavir inhibits hepatitis B virus(HBV) replication in HBV replication mice

作　　者：刘凤君[1,2] 刘丽[1] 蒋智[3] 刘聪[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感染病分子生物学研究室,四川成都610041 [2]川北医学院附属医院感染科,四川南充637000 [3]川北医学院附属医院急诊科,四川南充637000

出　　处：《基础医学与临床》2009年第10期1017-1020,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金(30571640);国家重点基础研究规划973计划(2007CB12900);2004年度CMB医学教育与科研基金项目基金(#88-486)

摘　　要：目的了解乙型肝炎病毒(HBV)复制型小鼠模型能否用于抗HBV药物的筛选。方法采用高压注射体内转染法将HBV复制型重组质粒pHBV4.1导入雄性BALB/c小鼠,转染后24h按体质量、年龄、血清HBeAg水平对小鼠进行配对,分为实验组和对照组(n=4),2组小鼠分别连续3d(每日1次)给恩替卡韦和生理盐水灌胃。最后1次给药后24h处死小鼠。分别用Northern、Southern杂交检测小鼠肝脏HBV mRNA和HBV DNA复制中间体;ELISA检测血清中HBeAg和HBsAg。结果重复2次实验的结果显示,实验组小鼠HBV DNA复制中间体水平明显低于对照组,而2组小鼠HBV mRNA、HBeAg和HBsAg水平无明显差异。结论恩替卡韦抑制HBV复制型小鼠体内HBV的复制,提示该小鼠模型可以用于抗HBV药物的初步筛选。Objective To investigate whether HBV replication mouse model can be used for selection of anti-HBV medicine. Methods HBV replication-competent plasmid pHBV4.1 was transferred into male BALB/C mice by hydrodynamics-based in vivo transfection. The mice were matched by body weight, age and serum level of Hepatitis B e antigen（HBeAg） and were devided into experiment group and control group （4 mice in each group） 24 h after transfection and then treated orally with entecavir or normal saline at interval of twenty four hours. HBV mRNA and HBV DNA replication intermediates in liver were analyzed by Northern and Southern Blot Hybridization, respective- ly. The serum HBsAg and HBeAg were detected by enzyme linked immunosorbentassay （ELISA）. Results The results of two indepent experiments showed that compared with the control animals, HBV DNA replicative interme diates dramatically decreased in the liver from the experiment mice . The levels of HBV mRNA from liver and the serum HBsAg and HBeAg, however, were not significantly different. Conclusion The inhibitory effect of entecavir on HBV was detected in the HBV replication mice, suggesting that the HBV replication mouse model can be used for selection of anti-HBV drugs.

关 键 词：恩替卡韦 乙型肝炎病毒 复制 动物模型 高压注射体内转染法 

分 类 号：R512.62[医药卫生—内科学]