不同修饰的左氧氟沙星体外抗乙型肝炎病毒的作用及其作用机理的研究

Inhibitory effects of Levofloxacin on hepatitis B virus in vitro

目的本文用2.2.15细胞研究不同修饰的左氧氟沙星(磺酸左氧氟沙星、左氧氟沙星、乳酸左氧氟沙星)体外抗乙型肝炎病毒的作用及其作用机理。方法以HBsAg、HBeAg及细胞存活率为观察指标,综合评价不同修饰的左氧氟沙星体外抗HBV效果,进一步用荧光定量PCR方法测细胞内HBV DNA、HBV RNA及细胞上清HBV DNA的拷贝数,推测药物体外抗乙型肝炎病毒的作用机理。结果结果提示磺酸左氧氟沙星对HBsAg和HBeAg的ID_(50)分别为63.1μg/ml及81.3μg/ml,CD_(50)为182.0μg/ml,TI>2。磺酸左氧氟沙星对细胞内、外HBVDNA及细胞内HBV RNA均有明显的剂量依赖型抑制作用(P<0.05)。结论磺酸左氧氟沙星有明显的抗HBV作用,对HBV抑制位点可能在HBV DNA水平。

Objective To investigate the inhibitory effects of Levofloxacin with different modifications on hepatitis B virus and their mechanism. Methods The survival cell rate was determined by MTT assay. HbsAg and HBeAg,were examined by radioimmunoassay. The value of TI (TI = CD50/ID50>CD50 is the drug concentration that reduces cell growth by 50% ; ID50 is the drug concentration that inhibits HBsAg or HBeAg secretion by 50%) was used to evaluate the effects of the drug on HBV. Based on the copies of extracellular HBV DNA, intracellular HBV RNA and HBV DNA tested by fluorescent quantitative PCR, we could speculate the mechanism of the drug against HBV. Results HBsAg and HBeAg ID50 of Levofloxacin sulphurate were 63. 1μg/ml and 81. 3μg/ml respectively. The CD50 was 182. 0μg/ml and TI>2. It inhibited extracellular HBV DNA, intracellular HBV RNA and HBV DNA in a dose-dependent manner (P<0. 05). Conclusion Levofloxacin sulphurate can block the replication and transcription through inhibiting HBV DNA.