苦参素对肝纤维化大鼠肝脏肌细胞增强因子2信号通路的影响

Interventional effect and mechanism of oxymatrine on myocyte enhancer factor 2 signaling pathway in rats with hepatic fibrosis

目的:探讨苦参素(OMT)抗肝纤维化的作用效果及对肝脏肌细胞增强因子2(MEF2)信号通路的影响。方法:采用皮下注射50%CCl 4的方法制备肝纤维化模型大鼠并对模型大鼠灌胃40 mg/kg OMT治疗,采用HE、Masson和免疫组织化学染色法检测大鼠肝组织损伤和纤维化程度,应用荧光定量PCR技术检测大鼠肝组织MEF2信号通路相关基因MEF2A和MEF2C表达水平。结果:通过HE、Masson染色证实成功制备了肝纤维化大鼠模型;免疫组织化学表明在肝纤维化大鼠肝组织中α-平滑肌肌动蛋白(α-SMA)高表达;荧光定量PCR结果显示在肝纤维化大鼠肝组织中MEF2A和MEF2C表达升高(P<0.05);同时,OMT可降低肝纤维化大鼠肝组织中MEF2A和MEF2C的表达水平(P<0.05)。结论:在肝纤维化模型大鼠中MEF2信号通路被激活,OMT抗肝纤维化作用可能部分是通过抑制MEF2信号通路的活化发挥作用的。

Objective:To investigate the effect of oxymatrine(OMT)on liver fibrosis and myocyte enhancer factor 2(MEF2)signaling pathway.Methods:Model rats of liver fibrosis was developed by subcutaneous injection of 50%CCl 4,and then treated with 40 mg/kg OMT.HE,Masson and immunohistochemical staining were used to detect liver injury and fibrosis in the rats,and fluorescent quantitative PCR was performed to measure the expression levels of MEF2A and MEF2C related genes in MEF2 signaling pathway.Results:HE and Masson staining verification indicated successful development of the rat model of hepatic fibrosis.Immunohistochemistry showed high expression ofα-smooth muscle actin(α-SMA)in the liver tissues of rats with hepatic fibrosis.Fluorescent quantitative PCR demonstrated that the expression of MEF2A and MEF2C was significantly increased in the liver tissue of rats with hepatic fibrosis(P<0.05)and OMT significantly decreased the expression of MEF2A and MEF2C(P<0.05).Conclusion:The MEF2 signaling pathway is activated in the model rats of liver fibrosis,and OMT anti-fibrosis may play a role in inhibiting the activation of MEF2 signaling pathway.