复方黄芪颗粒对肝纤维化大鼠肝脏基质金属蛋白酶-2、金属蛋白酶组织抑制因子-2蛋白表达的影响

Effects of compound granule of Huangqi on the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in experimental liver fibrosis rats

目的:探讨复方黄芪颗粒对肝纤维化大鼠肝脏基质金属蛋白酶-2(MMP-2)、金属蛋白酶组织抑制因子-2(TIMP-2)蛋白表达的影响。方法:应用Chevallier半定量计分系统,病理组织学观察等方法,结合细胞外基质(ECM)特殊染色动态变化观察,分析高、低剂量FFHQKL治疗猪血清诱导肝纤维化大鼠的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观察造模结束时以及药物治疗各时间段肝组织内MMP-2、TIMP-2表达量的变化。结果:与模型组比较,高、低剂量复方黄芪颗粒治疗第2个月、3个月结束时,大鼠肝组织Chevallier纤维化评分均明显减少(P<0.01)。复方黄芪颗粒高、低剂量治疗组大鼠在治疗第2个月、3个月结束时,TIMP-2蛋白表达明显减弱,MMP-2蛋白表达明显增强,与模型组比较差异有显著性意义(P<0.05)。结论:复方黄芪颗粒可以在蛋白水平增强MMP-2酶蛋白的表达,同时抑制TIMP-2酶蛋白的表达,促进ECM的降解,从而达到逆转肝纤维化的目的。

Objective： To investigate the effects of compound granule of Huangqi on the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in experimental liver fibrosis rats. 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 compound granule of Huangqi. By using immunohistochemical method, the dynamic changes in expression of MMP-2, TIMP-2 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 compound granule of Huangqi, 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-2 was significantly decreased and the expression of MMP- 2 was significantly increased 2, 3 months after the treatment in the high and low dosage groups of compound granule of Huangqi （ P 〈 0.05） . Conclusion： Compound aranule of Huangqi can increase the expression of MMP-2, down-regulate the expression of TIMP-2, accelerate the degradation of ECM and reverse liver fibrosis.