利莫那班对肝纤维化C57小鼠肝组织大麻素受体1及α-SMA表达的影响

Effects of Rimonabant on Cannabinoid Receptor 1 and α-Smooth Muscle Actin in C57 Mice with Experimental Hepatic Fibrosis

目的研究大麻素受体1(CB1)拮抗剂利莫那班对肝纤维化模型C57小鼠肝组织中CB1、α-平滑肌肌动蛋白(α-SMA)表达的影响,及其抗肝纤维化的作用机制。方法 30只C57小鼠随机分为3组,分别为正常对照组、模型对照组及利莫那班组,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。造模2周后于继续造模同时,正常对照组和模型对照组每天生理盐水灌胃,利莫那班组用利莫那班灌胃。第8周造模结束时处死小鼠,留取肝脏组织标本,分别进行HE和Masson三色染色,应用免疫组织化学方法检测肝组织中CB1和α-SMA的表达,并进行肝组织纤维化评分(S评分)。结果模型对照组和利莫那班组肝组织S评分、CB1和α-SMA阳性表达量均高于正常对照组(均P<0.05),利莫那班组均低于模型对照组(均P<0.05);正常对照组、模型对照组和利莫那班组CB1评分、α-SMA评分与S评分相互之间均呈正相关(均P<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,进而抑制肝星状细胞的增殖和激活,从而起到抗肝纤维化的作用。

Objective To study the effect of rimonabant, cannabinoid receptor 1（CB1） antagonist, on the expressions of CB1 andα-smooth muscle actin （α-SMA） in C57 mice with experimental hepatic fibrosis, and their mechanisms in liver fibrosis progression thereof. Methods Thirty C57 mice were randomly divided into three groups, normal control group, mod-el control group and model＋rimonabant group, 10 mice for each group. The mouse model of experimental hepatic fibrosis was induced by intraperitoneal injection with 10%CCl4 for two weeks. The normal saline was delivered by gavage daily in normal control group and model control group. Rimonabant was given to mice in model＋rimonabant group. Mice were sacri-ficed at the end of eight weeks. Samples of liver tissue were collected. The expressions of CB1 andα-SMA in liver tissue of mice were observed by immunohistochemical staining. The score of fibrosis stage （S） in liver tissue was also analyzed. Re-sults The positive expressions of CB1 andα-SMA and the score S were significantly higher in model control group and model＋rimonabant group than those in normal control group （P〈0.05）. The positive expressions of CB1 andα-SMA and the score S were significantly lower in rimonabant group than those in model control group （P〈0.05）. There were positive corre-lations in CB1,α-SMA and S scores between normal control group, model control group and model＋rimonabant group （P〈0.05）. Conclusion The activation of CB1 can promote the formation of liver fibrosis. The anti-fibrotic effect of rimonabant, CB1 antagonist, related with the inhibiting of the proliferation and activation of hepatic stellate cells （HSC）, and the inhibit-ing of the expression of CB1.