抗纤软肝颗粒对肝纤维化大鼠肝脏基质转换及肝窦毛细血管化的影响

Effects of Kangxian Ruangan Granule on Matrix Transition and Hepatic Sinusoid Capillatization in Experimental Rat Liver Fibrosis

目的:观察抗纤软肝颗粒对实验性肝纤维化时肝脏基质金属蛋白酶-1(MMP-1)、金属蛋白酶组织抑制因子-1(TIMP-1)以及肝窦毛细血管化的影响,探讨其防治肝纤维化的作用。方法:250ml/L CCl_4经大鼠皮下注射制备肝纤维化模型并同时给予秋水仙碱、小和大剂量抗纤软肝颗粒治疗,用光镜和电镜观察肝组织病理变化;免疫组织化学法检测肝组织Ⅰ、Ⅲ、Ⅳ型胶原、层粘蛋白(LM)原住杂交的方法检测MMP-1 mRNA、TIMP-1 mRNA。结果:抗纤软肝颗粒能促进MMP-1的表达(P<0.05),抑制TIMP-1的表达(P<0.01),促进Ⅰ、Ⅲ型胶原的降解(P<0.01);有效抑制Ⅳ型胶原、LM的生成和沉积(P<0.01),改善肝纤维化大鼠肝组织病理变化(P<0.01)。减轻肝窦毛细血管化程度。结论:抗纤软肝颗粒能促进MMP-1的表达,抑制TIMP-1的表达,促进胶原的降解,抑制肝窦毛细血管化的形成,从而产生抗肝纤维化的作用。

Objective: Through observing the effects of Kangxian Ruangan granule on MMP-1, TIMP-1 and hepatic sinusoid capitalization in the livers of experimental rats with hepatic fibrosis, to discuss its fuction of preventing and curing liver fibrosis. Methods: Rat models of the experimental liver fibrosis induced by CCl4 were established, colchicine and different dosages of kangxian Ruangan granule were given during the process of model making. Histopathological changes were examined by optical and electron microscopies. Collagen I , Ⅲ and Ⅳ , and LM in the hepatic tissues were detected by immunohistoche-mical techniques. MMP-1 mRNA and TIMP-1 mRNA were examined by in situ hybridization. Results: Kangqian ruangan granule could accelerate the expression of MMP-1 (P<0.05), inhibit the expression of TIMP-1 mRNA (P<0.01) and accelerate the degradation of both Collagen I and Collagen Ⅲ (P<0.01). It could also inhibit collagen Ⅳ and LM accumulation in the fibrotic livers (P<0.01), improve the Histopathological changes in hepatic tissues in experimental rat liver fibrosis (P<0.01) and attenuated the degrees of the hepatic sinusoid capillatization. Conclusion: Kangxian Ruangan Granule could accelerate the expression of MMP-1, inhibit the expression of TIMP-1 mRNA, accelerate the degradation of Collagen and inhibit the formation of hepatic sinusoid capillatization. It has a good anti-hepatic fibrosis fuction.