替比夫定对乙肝病毒转基因鼠孕期的影响及对母婴阻断的实验研究  

Study on Safety of Telbivudine in Treatment of Hepatitis B Virus Transgenic Mice with Pregnancy and Efficacy of Preventing HBV Mother-to-Child

作　　者：张庆英[1] 程海东[1] 蒋佩茹[2] 沈艳[2] 

机构地区：[1]复旦大学附属妇产科医院,上海200011 [2]复旦大学附属上海市公共卫生临床中心妇产科,上海201508

出　　处：《中国临床医学》2010年第2期201-204,共4页Chinese Journal of Clinical Medicine

基　　金：上海市重点学科建设项目子课题(编号:B117)

摘　　要：目的:研究乙型肝炎病毒(HBV)转基因鼠孕期应用抗病毒药替比夫定对母胎鼠安全性和母婴阻断的有效性。方法:33只HBV转基因雌鼠分为3组。交配当天至分娩当天,A组每天喂以0.9%氯化钠液,B组替比夫定600mg·kg-1.d-1灌胃,C组替比夫定1200mg·kg-1.d-1灌胃,另10只普通小鼠为对照组D组,每天替比夫定600mg·kg-1.d-1灌胃。交配当天、分娩当天抽血2次,酶联免疫法测乙型肝炎表面抗原(HBsAg)、荧光定量PCR法测乙肝病毒脱氧核糖核酸(HBVDNA)。观察4组雌鼠的妊娠生育状况及子鼠的生长发育情况,同时子鼠28d时检测HBsAg、HBVDNA,肝组织行免疫组化检查。结果:用药前后A组血清HBsAg浓度无显著性差异(P>0.05),B、C组血清HBsAg浓度有显著性差异(P<0.05)。3组雌鼠用药前后血清HBVDNA浓度无显著性差异。A组所生小鼠的血清HBVDNA、HBsAg与B组有显著性差异(P<0.05)。各组子鼠的生长发育指标均无显著性差异。B组和C组所生部分子鼠肝组织无HBsAg颗粒表达,部分子鼠肝组织HBsAg颗粒弱阳性表达。结论:孕期应用替比夫定对雌鼠子鼠的安全性的影响不明显,且对母婴阻断有效。Objective：To study the safety of Telbivudine for hepatitis B virus （HBV） transgenic mice with pregnancy and the efficacy of preventing HBV mother-to-child. Methods：Thirty-three transgenic mice replicating high levels of HBV were randomly allocated into 3 groups,each group of eleven mice. Pregnant HBV transgenic mice in experimental groups,Group A were given normal saline and Group B were given orally telbivudine （600mg/kg/d） from mating to delivery,Group C were given orally telbivudine （1200mg/ kg/d）.The changes of serum HBsAg,HBV DNA before and after the treatment were detected. At the same time,eleven C57BL /6J female mice （D） were given telbivudine （600mg/kg/d）.The safety indexes of pregnant mice,fetus and newborns in experimental groups and control groups were observed. Newborns were detected about the changes of serum HBsAg and HBV DNA. Liver tissue was examined by immunohistochemical method. Results：The average serum HBsAg titers from mice in experimental Group A was no significant difference between before and after the treatment （P0.05）,while Group B and Group C were lowered after drug treatment （P0.05）. The serum HBV DNA titers from mice in each experimental groups was no significant difference between before and after the treatment （P 0.05）. No significant abnormalities of live fetus was observed. The postnatal survival and weight of live pups were not different between the groups. The liver tissue of newborn was collected to detect negative HBsAg in the cells by immunohistochemical method.Conclusions：Effective telbivudine treatment during gestation can prevent HBV mother-to-child. It has no significant adverse effect on safety of pregnant mice and their offspring.

关 键 词：替比夫定 乙型肝炎病毒 小鼠 转基因 

分 类 号：R978.7[医药卫生—药品]