抗乙肝病毒新药Bay41-4109在HBV转基因小鼠中的药效学研究  

Pharmacodynamic study of Bay41-4109 in HBV transgenic mouse model

作　　者：李秀梅 陈阳述 刘光泽 黎经纬 陈媚娟 周军辉 孔祥平 

机构地区：[1]解放军458医院全军肝病中心、全军转基因动物重点实验室,广州510600

出　　处：《解放军医学杂志》2011年第9期893-896,共4页Medical Journal of Chinese People's Liberation Army

基　　金：“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十一五”课题资助(2008ZX10002-011)

摘　　要：目的研究抗乙肝病毒新药Bay41-4109在HBV转基因小鼠体内的药效学作用。方法 SPF级TgM(HBV D1.3)小鼠分为Bay41-4109组[30mg/(kg.d)],拉米夫定组[30mg/(kg.d)]和溶媒组(0.5%羧甲基纤维素钠)3组,每组32只。利用免疫组化分析HBV转基因小鼠肝组织HBcAg变化,定量PCR技术研究HBV转基因小鼠肝组织HBV DNA及血清HBV DNA的变化,并从血清转氨酶及体重指标分析该药物体内作用的安全性。结果给药第50天,Bay41-4109组HBcAg阳性细胞核个数、阳性细胞核平均面积、光密度比值三项指标均明显低于溶媒组(P<0.05);用药第64天(停药2周),各组间上述三项指标均无统计学差异。拉米夫定组各时间点上述指标与溶媒组之间均无明显差异(P>0.05)。但Bay41-4109对肝组织及血清HBV DNA未见明显作用。该药未对HBV转基因小鼠血清转氨酶及体重产生明显影响。结论 Bay41-4109可有效抑制HBV转基因小鼠肝组织HBcAg表达,且效果优于拉米夫定。Bay41-4109是一种安全性较好的抗乙肝新药,其作用机制不同于拉米夫定。Objective To study the pharmacodynamics of Bay41-4109,a novel anti-HBV compound,in HBV transgenic mouse model.Methods specific pathogen frce（SPF） level TgM（HBV D1.3）mice were divided into 3 groups： Bay41-4109 group [30mg/（kg·d）],lamivudine group [30mg/（kg·d）] and vehicle group（0.5% sodium carboxymethycellulose）,with 32 in each.Antiviral effect of Bay41-4109 was tested in HBV transgenic mice including the analysis of HBcAg changes in liver tissue by immunohistochemistry,and changes in HBV DNA in liver and serum by quantitative real time PCR analysis.Serum transaminase（ALT and AST） and body weight were assayed to evaluate the safety of the compound.Results Oral Bay41-4109 significantly reduced the number of HBV core antigen（HBcAg） positive cell nucleus,average area of HBcAg positive cell nucleus and the rate of OD compared with vehicle group after 50 days treatment（P0.05）.On the 64th day,all the three indicates showed no substantial difference in these three groups.Lamivudine treatment had no obvious effect on HBcAg compared with vehicle group（P0.05）.However,Bay41-4109 could not significantly reduce HBV-specific DNA in HBV transgenic mice,both in liver and plasma.No significant impact was found on ALT,AST and body weigh of Bay41-4109-treated mice.Conclusions Bay41-4109 can more effectively reduce cytoplasmic HBcAg in liver sections than lamivudine.It is suggested that Bay41-4109,a different mode of action from lamivudine,represents a promising anti-HBV drug candidate with good antiviral effect and safety.

关 键 词：抗病毒药 小鼠 转基因 肝炎病毒 乙型 

分 类 号：R512.62[医药卫生—内科学]