大麻素受体1、FAK mRNA在小鼠肝纤维化形成过程中肝组织中的表达及相互关系

Hepatic expression of CB1 in rats with fibrosis and the relationship with FAK

目的研究大麻素受体1(CB1)mRNA在肝纤维化形成过程中表达的变化,从基因转录水平探讨其与黏着斑激酶(FAK)的关系。方法采用10%四氯化碳腹腔注射制备肝纤维化模型,分别于造模第2、4、6、8周留取小鼠的肝组织及血清。通过肝组织病理对肝纤维化程度进行评分,荧光定量PCR检测CB1 mRNA和FAK mRNA水平,ELISA方法检测血清中转化生长因子(TGF)β1的含量。结果与正常对照组相比,各模型组小鼠肝组织中CB1 mRNA和FAK mRNA含量显著升高(P<0.05),而且随造模时间的延长,CB1 mRNA和FAK mRNA含量亦逐渐增高,各组之间差异有统计学意义(P<0.05)。CB1 mRNA的含量不但与肝纤维化评分呈显著正相关(r=0.747),而且与肝组织中FAK mRNA含量也呈显著正相关(r=0.907),P值均<0.01。各模型组小鼠血清中TGFβ1的水平随造模时间延长而不断升高,各组间差异具有统计学意义(P<0.05)。肝组织中CB1 mRNA的含量与血清TGFβ1水平呈显著正相关(r=0.542,P<0.01)。结论 CB1可能通过激活FAK,以磷脂酰肌醇-3-激酶(PI3K)通路诱导肝星状细胞(HSC)增殖并分泌大量TGFβ1,从而促进肝纤维化的形成。

Objective To evaluate hepatic expression of CB1 mRNA in rats during liver fibrogenesis and study the relationship between CB1 and FAK. Methods Liver fibrosis model was prepared by intraperitoneal injection of carbon tetrachloride （ 10% ）. Liver tissues and serum samples were collected at 2, 4, 6 and 8 week. The scores of fibrosis stage （S） were performed. The mRNA levels of CB1 mRNA and FAK were determined by quantitative RT - PCR. The levels of serum TGFβ1 were detected by ELISA. Results Compared with normal control group, CB1 mRNA and FAK mRNA levels in every model group were significantly increased （ P 〈 0.05 ）. With the modeling time pro- longed, CB1 and FAK mRNA levels gradually increased （P 〈 0.05 ）. CB1 mRNA level in liver tissue not only had correlation with the degree of liver fibrosis（r =0. 747, P 〈0. 01 ）, but also with FAK mRNA level in liver tissue（r =0. 907, P 〈0. 01 ）. With the modeling time prolonged, serum TGFβ1 level gradually increased （ P 〈 0.05 ）. CB1 mRNA level in liver tissue had positive correlation with serum TGFβ1 level （ r = 0. 542, P 〈 0.01 ）. Conclusion CB1 may promote the activation of FAK in rats with fibrosis, and induce HSC proliferation and secrete plentiful TGFβ1 by PI3K signal transduetion. CB1 may promote progression of liver fibrosis.