目的:研究在活血化淤基础上辅以软坚散节自制的双甲五灵冲剂对大鼠肝纤维化模型抗纤维化的治疗机制.方法:采用免疫诱导型肝纤维化大鼠模型,80只Wister大鼠,分为5组,A预防组造模同时开始喂食双甲五灵冲剂;B治疗组1在造模结束的同时开始喂食双甲五灵冲剂;C治疗组2在造模结束3mo后开始喂食双甲五灵冲剂;D秋水仙碱组在造模结束的同时开始喂食秋水仙碱;另设正常对照组10只.采用HE染色观察肝组织改变及Von-Gieson胶原纤维特殊染色以观察肝纤维化程度,并采用肝组织原位杂交及免疫组织化学染色观察大鼠肝脏组织中TIMP-1和TIMP-2mRNA及蛋白的表达强度.结果:免疫诱导型肝纤维化大鼠,在造模结束后肝组织学改变呈进行性加重,以造膜结束后3mo为著,其TIMP-1和TIMP-2mRNA及蛋白呈强阳性表达,而经双甲五灵冲剂治疗后的大鼠与模型组大鼠相比,肝组织结构明显好转,纤维组织明显减少,TIMP-1和TIMP-2mRNA及蛋白表达明显降低(P<0.05),并且其效果为:预防组效果最好,治疗1组较治疗2组效果好,即造模同时开始喂食双甲五灵冲剂最好,造模结束同时用药好于造模结束3mo后用药,三组均明显优于秋水仙碱组.结论:中药双甲五灵冲剂治疗肝纤维化的机制可能通过抑制TIMP-1和TIMP-2mRNA及蛋白的表达而降低对MMPs的抑制,从而有利于MMPs对细胞外基质的降解. Objective: To study the therapeutic mechanism of anti-fibrosis in hepatic fibrosis model induced by blood stasis and decoction supplemented by Ruanjian Sanjie. Methods: 80 rats were induced by immune-induced hepatic fibrosis. Wister rats, divided into 5 groups, A prevention group modeling began to feed Shuangjia Wuling granules; B treatment group 1 began to feed Shuangjia Wuling granules at the end of modeling; C treatment group 2 at the end of the modeling 3mo After the start of feeding Shuangjia Wuling granules; D colchicine group began to feed colchicine at the end of the model; another normal control group of 10. HE staining was used to observe the liver tissue changes and special staining of Von-Gieson collagen fibers Observe the degree of hepatic fibrosis, and observe the expression of TIMP-1 and TIMP-2 mRNA and protein in liver tissue by in situ hybridization and immunohistochemical staining. Results: Immune-induced hepatic fibrosis in rats After the end of the model, the hepatic histological changes were progressively aggravated, and the expression of TIMP-1 and TIMP-2 mRNA and protein were strongly positive at 3 months after the completion of membrane formation. Rats and models after treatment with Shuangjia Wuling Granules Compared with group rats, the structure of liver tissue was significantly improved, the fiber group Significantly reduced, TIMP-1 and TIMP-2 mRNA and protein expression was significantly reduced (P <0.05), and its effect is: the prevention group has the best effect, treatment group 1 is more effective than treatment group 2, that is, modeling began feeding double A Wuling granules were the best. At the end of the modeling, the use of the drug was better than the end of the modeling 3 months later. The three groups were significantly better than the colchicine group. Conclusion: The mechanism of Shuangjia Wuling Granules in treating liver fibrosis may be through inhibition of TIMP- 1 and TIMP-2 mRNA and protein expression and reduce the inhibition of MMPs, which is conducive to MMPs degradation of extracellular matrix.