耐干扰素的乙型肝炎病毒细胞模型的建立

发布时间：2018-05-24 14:23

本文选题：干扰素 + 乙型肝炎病毒　；参考：《中国药学杂志》2017年10期

【摘要】：目的建立耐干扰素的乙型肝炎病毒(HBV)细胞模型,为进一步探索HBV对干扰素产生耐药机制提供实验基础。方法应用HBV体外转染细胞株HepG2.2.15,采用干扰素α-2b(IFNα-2b)低浓度(10~70 u·mL~(-1))长期诱导,历时48周建立HepG2.2.15/IFNα-2b细胞系模型。然后给予最佳药效浓度IFNα-2b培养4 d,比较低剂量诱导前后细胞上清液中HBsAg、HBeAg、HBV DNA的变化。结果经低浓度IFNα-2b刺激12周后,50 u·mL~(-1)组对最佳药效浓度IFNα-2b的敏感性显著降低,与刺激前细胞比较,HBsAg、HBeAg、HBV DNA的抑制率分别降低了25.48%、8.40%和15.43%,认为50 u·mL~(-1)为最佳刺激浓度。经50 u·mL~(-1)IFNα-2b分别刺激12~48周,发现36周后HBsAg、HBeAg、HBV DNA抑制率下降最明显,与刺激前细胞比较,抑制率分别降低了38.64%、15.71%和30.17%,认为36周为最佳刺激时间。结论经IFNα-2b持续诱导可使HepG2.2.15对IFNα-2b产生部分耐药,其中50 u·mL~(-1)IFNα-2b持续诱导36周最易使之产生耐药。
[Abstract]:Objective to establish interferon resistant hepatitis B virus (HBV) cell model and provide experimental basis for further exploring the mechanism of interferon resistance of HBV. Methods HBV was transfected into HepG2.2.15 cell line in vitro. The model of 48 Zhou Jianli HepG2.2.15/IFN 伪 -2b cell line was induced by low concentration of IFN- 伪 -2b (1070u HepG2.2.15/IFN 伪 -2b) for a long time. Then, the best concentration of IFN 伪 -2b was cultured for 4 days, and the changes of HBV-HBeAg DNA in the supernatant of HBeAg were compared before and after low dose induction. Results after 12 weeks of stimulation with low concentration of IFN 伪 -2b, the sensitivity of IFN 伪 -2b to the best concentration of IFN 伪 -2b was significantly decreased, and the inhibition rate of HBV-HBV-HBe-2b was reduced by 25.48% 8.40% and 15.43%, respectively. It was considered that 50 u mL-1) was the best concentration of IFN 伪 -2b. After 50 u mL~(-1)IFN 伪 -2b was stimulated for 12 ~ 48 weeks, it was found that the inhibition rate of HBV-HBV DNA was the most obvious after 36 weeks, and the inhibition rate was reduced by 38.64% and 30.17%, respectively, compared with that before stimulation. It was considered that 36 weeks was the best stimulation time. Conclusion sustained induction of IFN 伪 -2b can induce partial resistance of HepG2.2.15 to IFN 伪 -2b, of which 50 u mL~(-1)IFN 伪 -2b is most likely to induce drug resistance for 36 weeks.
【作者单位】：安徽医科大学第三附属医院药学部;安徽医科大学药学院;
【基金】：国家自然科学基金资助项目(81470165)
【分类号】：R96

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