替比夫定对乙型肝炎病毒转基因鼠孕期安全性的实验研究  

Study on safety of telbivudine in treating hepatitis B virus infection in pregnant transgenic mice

作　　者：张庆英[1] 蒋佩茹[1] 沈艳[2] 程海东[3] 

机构地区：[1]上海市公共卫生临床中心妇产科上海市产科肝病监护中心,201508 [2]上海市公共卫生临床中心动物实验中心 [3]复旦大学附属妇产科医院产科

出　　处：《中华传染病杂志》2010年第3期139-143,共5页Chinese Journal of Infectious Diseases

基　　金：基金项目：上海市重点学科建设项目子课题（B117）

摘　　要：目的探讨HBV转基因鼠孕期应用抗病毒药替比夫定对降低HBV载量、HBsAg水平的有效性以及对母、胎鼠的安全性。方法33只HBV转基因雌鼠均分为3组，交配当天至分娩当天，HBVTg对照组每天喂0．9％氯化钠溶液，HBVTg—L与HBVTg—H实验组分别予替比夫定600和1200mg·kg-1·d-1灌胃。普通雌鼠11只为健康对照组，予替比夫定600mg·kg-1·d-1灌胃。交配当天、分娩当天采血，ELISA法测HBsAg，荧光定量PCR法测HBVDNA。观察4组雌鼠的妊娠生育状况及子鼠的生长发育情况，子鼠28d时检测HBsAg、HBVDNA。数据行方差分析、t检验和x2检验。结果HBVTg对照组雌鼠用药前后血清HBsAg水平差异无统计学意义（t=0．34，P〉O．05），HBV曙L和HBVTg-H实验组雌鼠血清HBsAg分别为（187．39±23．18）gg／L比（160．50±27．69）gg／L，（190．48±22．43）ug／L比（161．89±21．23）μg／L（t=2．91，t=3．16；均P〈0．05），用药前后血清HBVDNA水平差异无统计意义（P〉O．05）。HBVTg对照组、HBVTg-L与HBVT牙H实验组子鼠血清HBVDNA水平分别为（11．22±1．08）、（8．38±1．80）和（8．97±1．86）lg拷贝／mL（F=4．34，P〈0．05），HBsAg分别为（93．03±18．37）、（9．56±4．39）和（9．27±2．69）μg／L（F=18．11，P〈O．05）。各组子鼠的生长发育指标差异均无统计学意义（P〉0．05）。结论孕期应用替比夫定对母鼠子鼠的安全性无影响，由于HBV转基因鼠的种类、孕期短等原因，雌鼠血清HBsAg下降明显，对HBVDNA水平影响较小。Objective To investigate the safety and efficacy of telhivudine in treating hepatitis B virus （HBV） infection in pregnant transgenic mice. Methods Thirty-three transgenic mice with HBV DNA positive were evenly divided into 3 groups： HBV Tg-L group, HBV Tg-H group and HBV Tg group, which were treated with 600 mg·kg-1·d-1 telbivudine, 1200 mg·kg-1·d-1 telbivudine and 0. 9% sodium chloride intragastrically every day during the period from mating to delivery, respectively. Healthy control group （11 common mice） were treated with 600 mg ·kg-1·d-1 telbivudine. The changes of serum HBsAg titers and HBV DNA levels before and after treatment were determined. The titers of HBsAg were measured by enzyme-linked immunosorbent assay （ELISA）. The levels of HBV DNA were measured by fluorescent real-time polymerase chain reaction （PCR）. The safety indexes of pregnant mice, fetus and newborns in all experimental groups and control group were observed. Newborns were examined for the changes of serum HBsAg and HBV DNA. The data were compared using analysis of variance, t test and Z2 test. Results The mean serum HBsAg titers in HBV Tg group were not significantly changed before and after treatment （t = 0.34, P〉0. 05）. Serum HBsAg titers in HBV Tg L group and HBV Tg-H group were （187. 39 ± 23. 18） μg/L vs （160.50± 27. 69） μg/L, （190. 48±22. 43） μg/L vs （161. 89± 21. 23） μg/L before and after treatment, respectively （t=2.91, t= 3.16 ; both P〈0.05）. The mean serum HBV DNA levels in all experimental groups were not significantly different before and after treatment （P〉0.05）. The mean serum HBV DNA levels of the offspring mice in HBV Tg, HBV Tg group and HBV Tg-H group were （11.22±1.08）, （8.38±1.80） and （8.97±1.86） lg copy/mL, respectively （F-4.34, P〈0. 05）. The serum HBsAg titers of offspring mice were （93.03±18.37）, （9.56±4.39） and （9. 27±-2.69） μg/L, respectively （F=18.11, P〈0.05）. No significant abnormalities of live fetus were

关 键 词：核苷类 抗病毒药 肝炎病毒 乙型 小鼠 转基因 妊娠 动物 肝炎表面抗原 乙型 

分 类 号：R51[医药卫生—内科学]