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核酸类似物PNA在HepG 2.2.15细胞中对乙型肝炎病毒复制的抑制作用

PNA inhibits hepatitis B virus replication in 2.2.15 cell line

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【作者】 刘江霞宋武慧熊雅婷丁焕平袁正宏

【Author】 LIU Jiangxia1,SONG Wuhui1,XIONG Yating2,DING Huanping3,YUAN Zhenghong1,3(1 Key Laboratory of Medical Molecular Virology,Shanghai Medical College,Fudan University,Shanghai 200032,China;2 Nanjing Chang’ao Pharmaceutical Technology Co.,Ltd.,Nanjing 210022,China;3 Institutes of Biomedical Sciences,Fudan University, Shanghai 200032,China)

【机构】 复旦大学上海医学院医学分子病毒学重点实验室南京长澳医药科技有限公司复旦大学生物医学研究院

【摘要】 目的评价核酸类似物PNA在HepG2.2.15细胞中对乙型肝炎病毒复制的抑制作用。方法以HepG2.2.15细胞作为细胞模型,拉米夫定作为阳性对照药物。HepG 2.2.15细胞于药物处理14 d后,收集上清液及细胞。采用ELISA检测上清液中HBsAg和HBeAg含量,HBV荧光定量检测上清液和细胞内HBV DNA水平,CCK-8试剂盒检测药物对细胞的毒性作用。结果核酸类似物PNA与拉米夫定在浓度1.6~1 000μmol·L-1内对HepG 2.2.15细胞的毒性均较小。与药物未处理组比较,PNA和拉米夫定均可有效抑制细胞上清HBV DNA,半数抑制浓度(IC50)分别为0.05~0.10μmol·L-1和0.09~0.18μmol·L-1,两者之间差异无统计学意义。结论在体外细胞实验中,PNA对细胞的毒性小,与拉米夫定的安全指数相当;PNA对乙型肝炎病毒复制有较强的抑制作用,且具有一定时效量效关系,与拉米夫定的抑制强度相当。

【Abstract】 AIM To study the inhibitory effects of hepatiotis B virus(HBV) replication by PNA in HepG 2.2.15 cell line.METHODS Both positive drug lamivudin(3TC) and PNA were added in HepG 2.2.15 cells for 14 d respectively. Cell Counting Kit - 8 was used to detect the cell proliferation and drug toxicity.ELISA kit detected HBsAg and HBeAg in supernatant.HBV DNA copies were quantized by using HBV PCR quantitative fluorescence detection kit.RESULTS Both PNA and 3TC had little drug toxicity in HepG 2.2.15 cell line.Comparing to negative control,PNA could effectively reduce HBV DNA levels in supernatant.The ranges of IC50 for PNA were 0.05 - 0.10μmol·L-1,whereas the ranges of IC50 were 0.09 - 0.18μmol·L-1 after 3TC treatment.These results indicated PNA had the same efficacy and safety as positive drug 3TC.CONCLUSION PNA has little drug toxicity in HepG 2.2.15 cell line and can inhibit HBV replication.There is no significant difference between PNA and 3TC.

【关键词】 PNA乙型肝炎病毒抗病毒药物
【Key words】 PNAhepatitis B virusantiviral drug
【基金】 重大新药创制(编号2009ZX09303-006)
  • 【文献出处】 中国临床药学杂志 ,Chinese Journal of Clinical Pharmacy , 编辑部邮箱 ,2012年06期
  • 【分类号】R512.62
  • 【被引频次】2
  • 【下载频次】97
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