解剖学报

解剖学报 ›› 2014, Vol. 45 ›› Issue (5): 633-638.doi: 10.3969/j.issn.0529-1356.2014.05.009

• 细胞和分子生物学 • 上一篇    下一篇

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

张慧芹1 刘泽洲1 续畅1 刘新2 娄金丽2 李健1 牛建昭1 郝钰1*   

  1. 1. 北京中医药大学基础医学院免疫学教研室，北京 100029; 2. 首都医科大学附属北京佑安医院检验科，北京 100069
  • 收稿日期:2014-02-10 修回日期:2014-04-24 出版日期:2014-10-06 发布日期:2013-10-06
  • 通讯作者: 郝钰 E-mail:yuhao64@sina.com
  • 基金资助:

    雷公藤肝损伤的机制;教育部创新引智基地项目

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

ZHANG Hui-qin1 LIU Ze-zhou1 XU Chang1 LIU Xin2 LOU Jin-li2 LI Jian1 NIU Jian-zhao1 HAO Yu 1*   

  1. 1. Department of Immunology,College of Basic Medicine, Beijing University of Traditional Chinese Medicine,Beijing 100029, China; 2. Clinical Laboratory, Beijing Youan Hospital, Capital University of Medicine, Beijing 100069, China
  • Received:2014-02-10 Revised:2014-04-24 Online:2014-10-06 Published:2013-10-06
  • Contact: Hao Yu E-mail:yuhao64@sina.com

摘要：

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。

关键词: 小檗碱, 非酒精性脂肪性肝炎, 巨噬细胞, 表型转化, 流式细胞术, 小鼠

Abstract:

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 M1 type macrophages and increased M2 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.

Key words: Berberine, Non-alcholic steatohepatitis, Macrophage, Phenotype transformation, Flow cytometry, Mouse