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利莫那班对肝纤维化模型C57小鼠肝组织大麻素受体 1及α-SMA表达的影响

叶立红   

  1. 石家庄市第五医院
  • 收稿日期:2013-09-17 修回日期:2013-12-14 出版日期:2014-05-15 发布日期:2014-05-15
  • 通讯作者: 叶立红

Infection of Rimonabant for Cannabinoid receptor 1 and α-smooth muscle actinof C57 mice with experimental hepatic fibrosis

  • Received:2013-09-17 Revised:2013-12-14 Published:2014-05-15 Online:2014-05-15

摘要: [摘要]目的:研究CB1拮抗剂利莫那班对肝纤维化模型C57小鼠肝组织中大麻素受体1(CB1)及α-SMA的影响,分析利莫那班在肝纤维化进展中的作用机制。方法: 30只C57小鼠随机分为3组,分别为正常对照组、模型对照组及模型利莫那班治疗组,每组10只。采用四氯化碳腹腔注射诱导形成小鼠肝纤维化模型。第6周结束时处死小鼠,留取肝脏组织标本,应用免疫组织化学染色方法检测肝组织中CB1和α-SMA的表达,并进行肝组织纤维化评分(S)。结果: 模型对照组和模型莫那班治疗组肝组织肝纤维化评分、CB1和α-SMA阳性表达量均高显著于正常对照组,差异均具有统计学意义(P<0.05);模型利莫那班治疗组肝组织CB1和α-SMA阳性表达量和纤维化评分较模型对照组均明显降低,差异具有统计学意义(P<0.05);各实验组小鼠CB1、α-SMA和S评分相关性分析显示,正常对照组、模型对照组和模型利莫那班治疗组CB1评分、α-SMA评分与S评分相互之间均具有显著相关性(P均<0.05)。结论:肝组织CB1的激活可促进肝纤维化的形成,CB1拮抗剂利莫那班通过抑制CB1表达,进而抑制HSC的增殖和激活,从而起到抗肝纤维化的作用。

关键词: 利莫那班, 大麻素受体1, α-平滑肌肌动蛋白(α-SMA), 肝纤维化, 动物模型

Abstract: [Abstract] Objective To study the effect of Rimonabant for cannabinoid receptor 1 andα-SMA of C57 mice with experimental hepatic fibrosis,Analysis the mechanism of action of rimonabant in Liver fibrosis progression . Methods thirty C57 mice were randomly divided into three groups, i.e. normal control group, model control group, model rimonabant group. There were 10 mice in every group. C57 mice with experimental hepatic fibrosis were induced by intraperitoneal injection of 10% CCl4. Mice were sacrificed at the end of six weeks , liver tissue were Specimened. The expression of CB1 andα-SMA in liver tissue of mice was observed by immune histochemical technique. The score of fibrosis stage (S) in liver tissue were also analyzed. Results The expression of CB1 andα-SMA and the score of fibrosis in model groups and model rimonabant group were significantly higher than those in normal control group (P<0.05), the expression of CB1 andα-SMA and the score of fibrosis in model groups were significantly lower than those in model rimonabant group (P<0.05), while Correlation analysis Indicate that there were correlative obvirously in the score of CB1、α-SMA and the fibrosis in each experiment group(P <0.05) .Conclusion The activation of CB1 can promote the formation of liver fibrosis, Rimonabant can Inhibit the proliferation and activation of HSC by inhibit expression of CB1, so have effect of anti hepatic fibrosis.

Key words: Rimonabant, cannabinoid receptor 1, α-smooth muscle actin, liver fibrosis, animal model