软肝缩脾丸对肝纤维化大鼠TIMP-1、2及Ⅰ、Ⅲ型胶原mRNA及蛋白表达的影响

Effect of Ruangansuopiwan on the Expression of Tissue inhibitor of Metalloprot-einase (TIMP-1 and TIMP-2) and Collagen Ⅰ and Collagen Ⅲ in the Liver of Rats with Hepatic Fibrosis

目的 观察软肝缩脾丸对纤维化大鼠肝脏基质金属蛋白酶组织抑制因子 -1、2 (TIMP -1、TIMP -2 )及Ⅰ、Ⅲ型胶原mRNA及蛋白表达的影响 ,从胶原降解的角度探索中药抗肝纤维化的可能机理。方法 制备大鼠肝纤维化模型 ,并给予软肝缩脾丸治疗 ;用原位杂交和免疫组化的方法分别测定TIMP -1、TIMP -2及Ⅰ、Ⅲ型胶原的mRNA和蛋白表达。结果 CCl4模型组TIMP -1、TIMP -2 ,Ⅰ、Ⅲ型胶原mRNA及蛋白水平明显高于治疗组。正常组大鼠肝组织无一例阳性。结论 TIMP -1、TIMP -2与肝纤维化形成密切相关 ,软肝缩脾丸可以抑制纤维化肝脏TIMP -1、TIMP -2的表达 ,从而增强间质胶原酶的活性 ,促进Ⅰ、Ⅲ型胶原的降解 ,产生抗肝纤维化作用。

Aim To study the effect of Rangansuopiwan on the expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2) and collagen Ⅰ and collagen Ⅲ in the liver of rats with hepatic fibrosis Methods Normal and hepatic fibrosis liver samples were obtained from CCl4 damaged rats underwent Rangansuopiwan treatment. Immunohistochemistry and in situ hybridization were used to detect the transcripts or expression of TIMP-1, TIMP-2, collagen Ⅰ and collagen Ⅲ in the liver tissues , respectively.Results The expression of TIMP-1,TIMP-2, collagen Ⅰ and collagen Ⅲ mRNA in CCl4 models was significantly higher than that in treatment group.and no expression of them in normal group.Conclusion The study shows that TIMP-1 and TIMP-2 closely participate in hepatic fibrosis in rats. Ruangansuopiwan can downregulate the expression of TIMP-1 and TIMP-2, and reduce the generation of collagenⅠ and collagen Ⅲ in the liver of rats.