蛋白酶活化受体2在大鼠胆汁淤积性肝纤维化肝组织中的表达及其意义

Differential expression of protease-activated receptor 2 in a bile duct ligation-induced rat model of liver fibrosis

目的观察胆汁淤积陛肝纤维化大鼠肝组织中蛋白酶活化受体2（PAR2）的动态变化，探讨其在肝纤维化形成中的意义。方法建立大鼠胆汁淤积陛肝纤维化模型，同时设立假手术组和正常对照组，Westernblot及RT-PCR检测术后2、4、6、8周肝组织中PAR2蛋白及mRNA的表达水平，并分析其与I、Ⅲ型胶原表达水平的关系。对数据进行重复测量资料的方差分析。结果肝纤维化组大鼠2周时即可见PAR2mRNA及蛋白水平升高，随着肝纤维化时间的延长，4～6周时其表达水平进一步升高护〈0．05），8周时达高峰（相对表达量分别为1．62±0．11、47．6±2．8，P〈0．01）。I、Ⅲ型胶原蛋白表达水平也随着肝纤维化程度的加重而升高，6～8周时达高峰（相对表达量均为65．6±2．7），且与PAR2的表达水平呈一致陛。结论PAR,在胆汁淤积陛肝纤维化中的动态表达可能参与并促进肝纤维化的形成和发展。

Objective To observe the dynamic change in expression of protease-activated receptor 2 （PAR2） during onset and progression of liver fibrosis by using a rat model. Methods A cholestatic liver fibrosis model was established in Sprague-Dawley rats （aged 8-9 weeks, body weight 350 - 400 g） by bile duct ligation surgery. Rats receiving a sham operation and unoperated rats served as the negative and normal control groups, respectively. At baseline （pre-surgery） and post-surgery weeks 2, 4, 6, and 8, five rats from each group were sacrificed for whole liver resection. The protein and mRNA expressions of PAR2 and collagen I/Ⅲ were detected by western blotting and RT-PCR, respectively. Betwean-group differences were assessed by analysis of variance testing. Results At post-surgery week 2, the liver fibrosis group showed higher expression of PAR2 mRNA and protein than either control group. The expression levels of PARs continued to rise over time in the liver fibrosis group （peaking at week 8）, and were significantly higher than those detected in the control groups （weeks 4-6： P 〈 0.05; week 8, P 〈 0.05）. A similar trend was observed for the expression of collagen I/Ⅲ. Conclusion Dynamic expression of PARs observed in a cholestatic liver fibrosis rat model may indicate a role for this factor in the formation of liver fibrosis.