小檗碱对胆碱-蛋氨酸缺乏饮食诱导非酒精性脂肪性肝炎小鼠肝组织巨噬细胞表型转化的调节作用

Regulating effect of berberine on macrophage phenotype transformation in hepatic tissue of mice with methionine-choline deficiency diet induced non-alcoholic steatohepatitis

目的观察小檗碱对胆碱-蛋氨酸缺乏(MCD)饮食诱导非酒精性脂肪性肝炎(NASH)模型小鼠肝组织巨噬细胞M1、M2表型转化的作用。方法雄性C57BL/6小鼠40只随机分为4组(每组10只):正常组(饲喂常规饲料),模型组(饲喂MCD饲料),罗格列酮干预组(30mg/kg)和小檗碱干预组(150mg/kg),采用预防给药方式,连续2周。通过组织病理学评分评估动物模型及药物疗效;采用ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-6)及IL-10水平;流式细胞术检测肝组织中M1、M2型巨噬细胞的数量和比值。结果罗格列酮和小檗碱可显著改善MCD饮食诱导小鼠NASH的病理程度,显著下调血清中TNF-α水平(P<0.05),显著上调血清中IL-10水平(P<0.05),显著降低肝组织中M1型巨噬细胞及增加M2型巨噬细胞的数量,降低M1/M2比值(P<0.01)。结论小檗碱对MCD饮食诱导小鼠NASH有较好改善作用,其部分药理机制为:调节肝组织中巨噬细胞表型转化,增加M2型巨噬细胞比例,上调抗炎细胞因子的分泌。

Objective To determine the efficacy of berberine in the treatment of non-alcoholic steatohepatitis （ NASH） , and to investigate the regulating effect on macrophage phenotype transformation in hepatic tissue on methionine -choline deficiency （MCD） diet induced NASH mice.Methods Fourty male C57BL/6 mice were randomly divided into 4 groups （10 mice per group）： the normal group （fed with normal diet）, the NASH model group （fed with MCD diet）, rosiglitazone treatment group （30mg/kg） and berberine treatment group （150mg/kg）.Drugs were adopted in the preventive intervention method for 2 weeks.The hepatic histopathological method was adopted to evaluate the drug therapeutic effect.The serum levels of tumor necrosis factor-α（TNF-α）, interleukin（IL）-6, and IL-10 were examined with ELISA method.M1 and M2 phenotype were detected by flow cytometry .Results The results showed berberine improved the degree of hepatic histopathology .Berberine not only reduced the level of TNF-α, but also increased the level of IL-10 in serum on NASH mice significantly （ P 〈0.05 ） . Flow cytometry data indicated that berberine decreased M 1 type macrophages and increased M 2 type macrophages in liver tissue .The ratio of M1/M2 was significantly decreased in berberine and rosiglitazone treated group （ P 〈0.01 ） .Conclusion Berberine may improve the hepatic pathological process in MCD diet induced NASH model possibly through modulating macrophage phenotype transformation , i.e.The ratio of M2 type is more than M1 type in hepatic tissue , and increasing anti-inflammatory cytokines .