阿的福韦在鸭乙型肝炎模型及2.2.15细胞中抗乙型肝炎病毒的药效研究  

Therapeutic effect of adefovir anti-duck hepatitis B virus in vivo and anti-HBV activity in vitro (2.2.15 cells)

作　　者：陈压西[1] 黄爱龙[1] 郭晖[1] 齐珍元[1] 

机构地区：[1]重庆医科大学病毒性肝炎研究所,重庆400010

出　　处：《重庆医科大学学报》2004年第5期618-621,共4页Journal of Chongqing Medical University

摘　　要：目的 :观察阿的福韦体内抗鸭乙型肝炎病毒 (DHBV)的作用及体外抗乙型肝炎病毒 (HBV)效果。方法 :采用鸭乙型肝炎动物模型 ,用阿的福韦口服治疗 10天 ,检测用药前后血清中的DHBVDNA、DHBsAg ,并取肝脏样本提取总DNA ,作SouthernBlot分析。此外 ,以 2 .2 .15细胞为靶细胞 ,给药后通过检测细胞培养液中HBsAg、HBeAg和HBVDNA观察阿的福韦抗HBV效果。结果 :阿的福韦各剂量组用药后均能使血清中的DHBVDNA显著降低或极显著降低 (P <0 .0 5或P <0 .0 1) ,但停药后有DHBVDNA回升现象 ;用药前后DHBsAg无明显改变。肝组织SouthernBlot分析亦显示用药后肝脏中DHBVDNA有明显降低 ,停药后DHBVDNA反跳明显。大剂量阿的福韦加入细胞培养 12天 ,对HBsAg抑制率为 17.0 1% ,对HBeAg抑制率为 2 6 .80 % ,对HBVDNA抑制率为 2 6 .92 %。结论 :阿的福韦在鸭体内有抗鸭乙型肝炎病毒的作用 ,但停药后DHBVDNA有“反跳”现象 ;Objective:To study the therapeutic effect of the purine nucleoside analog adefovir against duck hepatitis virus (DHBV) in vivo and anti-HBV activity in vitro.Methods:The Chongqing duck hepatitis B animal model was treated with adefovir by intragastric administration once a day for 10 days.DHBV DNA in serum and liver were monitored by serum dot-blot hybridization and Southern blot.DHBsAg in serum was detected simultaneously by ELISA.The anti-HBV activity of adefovir was observed in 2.2.15 cells (human hepatocellular carcinoma cells stably transfected with HBV).Results:Adefovir could significantly reduce DHBV DNA level.After stopping the treatment for 3 days,DHBV DNA level in serum and liver returned significantly.The O.D values of DHBsAg in duck serum did not change at the period of the treatment.After 12 days of continuous exposure to adefovir at the concentration of 20μg/ml in vitro culture,the inhibitions of HBsAg,HBeAg,HBV DNA were 17.01%,26.80%,and 26.92% respectively.Conclusion:The study confirms the safety and potent dose-dependent antihepadnaviral activity of adefovir in vivo.The anti-HBV effect is not demonstrated in 2.2.15 cells.

关 键 词：阿的福韦 鸭乙型肝炎病毒 动物模型 2.2.15细胞 

分 类 号：R512.6[医药卫生—内科学]