氧化苦参碱联合拉米夫定对慢性乙型肝炎患者TLR9信号通路的影响

Effects of oxymatrine combined with lamivudine on TLR9 signal pathway in patients with chronic hepatitis B

目的观察氧化苦参碱联合拉米夫定对慢性乙型肝炎患者TLR9信号通路的影响,旨在探讨氧化苦参碱治疗慢性乙型肝炎的可能机制。方法选取诊治的慢性乙型肝炎患者120例,随机分为对照组和观察组,每组60例,对照组在常规治疗基础上给予拉米夫定治疗,观察组在对照组基础上加用氧化苦参碱治疗,疗程为6个月,比较2组临床疗效。采用Real time-PCR和Western blot测定外周血单个核细胞(PBMCs)中TLR9信号通路关键信号分子(TLR9、My D88、TRAF6、IRF7)mRNA和蛋白表达。采用酶联免疫吸附实验(ELISA)测定血清抗病毒细胞因子[干扰素(IFN)-α、IFN-γ、肿瘤坏死因子-α(TNF-α)]水平。结果观察组和对照组总有效率分别为96.67%、70.0%,观察组总有效率显著高于对照组,差异有统计学意义(P<0.05)。与治疗前比较,治疗后2组TLR9、My D88、TRAF6、IRF7 mRNA和蛋白表达及IFN-α、IFN-γ、TNF-α水平均显著升高,差异有统计学意义(P<0.05),观察组升高程度更明显,与对照组比较差异有统计学意义(P<0.05)。结论氧化苦参碱联合拉米夫定能够发挥有效的抗HBV作用,其机制与激活TLR9信号通路、诱导抗病毒细胞因子释放有关。

Objective To investigate the effects of oxymatrine combined with lamivudine on TLR9 signal pathway in patients with chronic hepatitis B （CHB） in order to explore possible action mechanism of oxymatrine in treatment of CHB. Methods One hundred and twenty patients with CHB in our hospital were randomly divided into control group and observation group, with 60 patients in each group. The patients in control group, on the routine therapy, were given iamivudine, however,the patients in observation group , on the basis of control group,were treated by oxymatrine,with a treatment course of 6 months for both groups. The therapeutic effects were observed and compared between two groups. Moreover the expression levels of TLR9 ,MyD88, TRAF6, IRF7 mRNA and protein in peripheral blood mononuclear cell （PBMCs） were detected by Real time-PCR and Western Blot, respectively, and the serum levels of IFN-a, IFN-Y,TNF-a were detected by enzyme linked immunosorbent assay （ELISA）. Results The total effective rates in observation group and control group were 96.67% and 70.0%, respectively, and there was a significant difference between two groups （ P 〈 0.05）. As compared with those before treatment, the expression levels of TLR9, MyD88, TRAF6, IRF7 mRNA and proteins, the serum levels of IFN-a, IFN-w, TNF-a were significantly increased after treatment in both groups （ P 〈 0.05 ）, furthermore, the increase degree in observation group was more significant than that in control group （ P 〈 0.05 ）. Conclusion Oxymatrine combined with lamivudine is effective for CHB, with an obvious anti-HBV role, and its action mechanism may be related to activating TLR9 signal pathwaY and inducing the release of antiviral cytokines.