复方黄芪颗粒抗肝纤维化机制的实验研究

目的:探讨复方黄芪颗粒(FFHQKL)有无抗肝纤维化作用及作用机制.方法:应用Chevallier半定量计分系统,病理组织学观察,结合细胞外基质(ECM)特殊染色动态观察高、低剂量FFHQKL治疗猪血清诱导肝纤维化模型后各时间段肝组织学及ECM量的变化,评估复方黄芪颗粒的抗肝纤维化疗效;应用免疫组织化学染色方法观察造模结束时以及药物治疗各时间段肝组织内基质金属蛋白酶-13(MMP-13)及其抑制剂(TIMP-1)表达量的变化.结果:与模型组比较,高、低剂量FFHQKL治疗2个月、3个月结束时,肝组织Chevallier纤维化评分均明显减少(P＜0.01).FFHQKL高、低剂量治疗组在治疗第2个月结束时,TIMP-1蛋白表达明显减弱,MMP-13蛋白表达明显增强,治疗第3个月结束时,上述改变更加显著,与模型组比较差异有显著性意义(P＜0.05或P＜0.01).结论:FFHQKL可在蛋白水平增强MMP-13酶蛋白的表达,同时抑制TIMP-1酶蛋白的表达,促进ECM的降解,从而达到逆转肝纤维化之疗效.

Experimental Studies of FFHQKL on Anti-hepatic Fibrosis in Rats

Objective:In order to evaluate the curative effect and explore the possible mechanism of FFHQKL on anti-hepatic fibrosis.Methods:The rats was given intraperitoneal injection of porcine serum twice a week to establish the model of experimental immuno-damaged hepatic fibrosis. By using HE staining and special staining, the dynamical changes of hepatic histology of rats were observed to determine the curative effect of FFHQKL. By using immunohistochemical method, the dynamic changes in expression of MMP-13, TIMP-1 were determined in liver tissues from the experimental rats.Results:Compared with the control group, in which rats with hepatic fibrosis were not treated with FFHQKL, the histological examination of rat livers in the treatment groups showed that the total scores of hepatic fibrosis in treatment groups with high and low dosage were significantly decreased 2,3 months after the treatment(P<0.01). With the decreased degree of liver fibrosis, the expression of TIMP-1 was significantly decreased and the expression of MMP-13 was significantly increased 2,3 months after the treatment in the high and low dosage groups of FFHQKL(P<0.05 or P<0.01).Conclusion:[WTBZ] FFHQKL could increase the expression of MMP-13,down-regulate the expression of TIMP-1, accelerate the degradation of ECM and reverse liver fibrosis.