肝靶向干扰素对HBV转基因小鼠JAK-STAT信号通路基因表达的影响

摘要

目的：研究肝靶向干扰素（ interferon-circumsporozoite protein，IFN-CSP）在HBV转基因小鼠中的抗HBV分子机制。方法 Balb／c-HBV转基因小鼠随机分为3组：Control组（给予生理盐水），IFNα2b组（给予普通干扰素IFN α2b 103 U／g），IFN-CSP组（给予IFN-CSP 102 U／g），另设普通正常Balb／C小鼠组（Normal）。小鼠经肌肉注射给药4周后，抽提肝组织总RNA，Real-time PCR检测小鼠肝组织中STAT1、STAT2、IRF-9、OAS1基因相对表达量。结果与正常小鼠对照组和模型组比较，IFN-CSP组和IFN α2b组STAT1，STAT2，IRF-9，OAS1基因表达均显著上调（P＜0.01），IFN-CSP的诱导效果明显强于IFN α2b（P＜0.05）。结论 IFN-CSP在HBV转基因小鼠中的抗HBV作用可能与其影响JAK-STAT信号通路中STAT1、STAT2、IRF-9、OAS1基因的表达有关，为其进一步的应用开发提供了实验依据。%Objective To investigate the anti-HBV molecular mechanisms of liver targeting interferon ( IFN-CSP ) in Balb/c-HBV transgenic mice.Methods Balb/c-HBV transgenic mice were randomly divided into 3 groups.Control group (treated with physiological saline), IFN α2b group (treated with 103 U/g IFN α2b), IFN-CSP group (treated with 102 U/g IFN-CSP).Another group of the non-transgenic mice were used as the Normal group.Each mouse was intramuscular injected with 50 μL dose once a day for 4 weeks.Total RNA of mice liver were extracted, and STAT1, STAT2, IRF-9, OAS1 gene expression of JAK-STAT signaling pathway were analyzed by real-time PCR.Results IFN α2b and IFN-CSP can significantly up regulate the expression of STAT1, STAT2, IRF-9, OAS1 gene of JAK-STAT signaling pathway (P<0.01).The induce effects of IFN-CSP on STAT1, STAT2, IRF-9, OAS1 were significantly better than that of IFN α2b (P<0.05).Conclusion The anti-HBV molecular mechanisms of liver targeting interferon (IFN-CSP) in Balb/c-HBV transgenic mice maybe related to regulate the expression of STAT1, STAT2, IRF-9, OAS1 gene of JAK-STAT signaling pathway.These results will lay a basis for the application of recombinant liver-targeting interferon.