肝纤维化大鼠TGF-β1与TIMP-1 mRNA的表达及补肾柔肝方的治疗作用

目的:探讨中药复方补肾柔肝方对二甲基亚硝胺(dimethylnitrosamine,DMN)诱导大鼠肝纤维化后肝脏组织金属蛋白酶抑制因子1(tissue inhibitor of metalloproteinase-1,TIMP-1)和转化生长因子β1(transforming growth factor-beta 1,TGF-β1)的影响,以了解其对肝纤维化的治疗作用和分子机制.方法:雄性Wistar大鼠40只,随机分为正常对照组、模型组和治疗组,对模型组和治疗组运用DMN诱导大鼠肝纤维化.治疗组在造模4周后给予补肾柔肝方灌胃,剂量10 g·kg-1·d,共治疗4周.第8周末处死全部大鼠,对肝组织进行HE和天狼猩红染色观察,并采用RT-PCR半定量方法,检测大鼠肝组织TIMP-1及TGF-β1mRNA的表达水平.结果:肝组织病理学研究结果显示DMN可以成功诱导大鼠肝纤维化,模型组肝组织TIMP-1和TGF-β1mRNA表达明显增强,中药复方治疗组与模型组相比明显减弱,而正常对照组表达较少.结论:TIMP-1与TGF-β1mRNA的表达与肝纤维化的发生密切相关,中药复方补肾柔肝方对肝纤维化大鼠肝组织TIMP-1及TGF-β1具有明显的抑制作用,可达到抗肝纤维化的作用.

Expression of TIMP-1 and TGF-β1 mRNA in hepatic fibrosis rats and the therapeutic effects of Bushen Rougan Recipe

OBJECTIVE: To study the expression of TIMP-1 and TGF-beta1 mRNA in hepatic fibrosis rats and the therapeutic effects of Bushen Rougan Recipe (BSRGR). METHODS: Hepatic fibrosis was induced in rats by dimethylnitrosamine (DMN). The rats' hepatic tissue was studied by HE staining and Sirius red staining. The rats were divided into normal control group, fibrosis model group and BSRGR treated group (10 g.kg(-1).d(-1), i.g. for 4 weeks). At last, TIMP-1 and TGF-beta1 mRNA were detected by RT-PCR. RESULTS: Pathological study showed that hepatic fibrosis was successfully induced by DMN in rats. The expression quantity of TIMP-1 and TGF-beta1 mRNA were the most in the fibrosis model group, the second in the BSRGR treated group, and the least in the normal control group. CONCLUSION: The expression of TIMP-1 and TGF-beta1 mRNA was increased in the hepatic fibrosis rats, and this is one possible mechanism of hepatic fibrosis. BSRGR can inhibit the advancement of hepatic fibrosis.