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活血化瘀类中药对实验性血吸虫肝纤维化兔肝组织金属蛋白酶-1及其抑制因子-1mRNA表达的影响 被引量:5

Experimental Study of Effect of Blood-activating and Stasis-eliminating Drugs on Expression of Matrix Metalloproteinase-1 (MMP-1) mRNA and Tissue Inhibitor of MMP-1 mRNA in Rabbits with Schistosomiosis Hepatic Fibrosis
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摘要 观察活血化瘀类中药对肝组织金属蛋白酶—1(MMP-1)及其抑制因子-1(TIMP-1)mRNA表达的影响,以及对金属蛋白酶-2(MMP-2)蛋白质表达的影响,从胶原降解的角度探讨中药抗纤维化的机理。方法:用血吸虫尾蚴120±1条经皮感染新西兰白兔,3个月后经病理证实已形成典型血吸虫肝纤维化,实验动物分4组,每组8只,一组灌服中药,一组灌服秋水仙碱,病理对照组和正常对照组灌服生理盐水。3个月后处死动物,取肝组织切片,采取原位杂交法检测MMP-1和TIMP-1mRNA的表达,用免疫组化法检测MMP-2蛋白的表达,并作Ⅰ、Ⅳ型胶原的免疫组化以及天狼红胶原染色。结果:与病理对照组相比,活血化瘀类中药和秋水仙碱治疗组,肝组织胶原蛋白总含量,Ⅰ、Ⅳ型胶原蛋白含量均显著减少。活血化瘀类中药组,MMP-1mRNA表达明显增加,TIMP-1mRNA的表达明显减少,MMP-2蛋白表达无显著差异。秋水仙碱组,TIMP-1mRNA的表达明显减少,MMP-1、MMP-2的表达无明显差异。结论:活血化瘀类中药抗纤维化的作用机理除了减少胶原蛋白的合成外,还与其降低MMP组织抑制因子的表达,增加金属蛋白酶的活性,促进间质胶原蛋白的分解有关。 To study the impact of blood-activating and stasis-eliminating drugs (BASED) on the liver fi- brosis and it's possible mechanism in the way of degradation of collagen by observing the effect of BASED on the expression of matrix metalloproteinase-1 (MMP-1)mRNA and tissue inhibitor of matrix metalloproteinase- (TIMP-1) ImRNA and protein of matrix metalloproteinase-2 (MMP-2) in rabbits with liver fibrosis induced by schistosoma japonicum. Methods: The rabbits were randomly divided into normal control group, liver fibrosis model group, the group treated with BASED and the group with Colchicine. At the end of experiment, the liver tissues were studied by in situ hybridization for expression of MMP-1mRNA and TIMP-1 mRNA, for type Ⅰ , Ⅳ collagen and MMP-2 by immunohistochemical method. Meanwhile the total collagen was detected by Sirius red staining. Results: The total content of collagen and contents of type Ⅰ, Ⅳ collagen in the group with BASED or the group with Colchicine were significantly lower than those in the normal control group. The expression of MMP-1 mRNA was significantly higher, the expression of TIMP-1 mRNA was significantly lower in the group treated with BASED than those in the model group. But there was not difference about MMP-2 protein expression between the two groups. The expression of TIMP-1 mRNA was significantly lower. There were not differences in expressions of MMP-1 mRNA and MMP-2 proteins between groups treated with Colchicine and model group. Conclusion: The anti-fibrosis effect of BASED may be relative to increase of MMP-lmRNA expression and decrease of TIMP-1 mRNA expression, which promotes the degradation of collagen.
出处 《中西医结合肝病杂志》 CAS 2001年第6期339-342,共4页 Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
关键词 金属蛋白酶-1 金属蛋白酶组织抑制因子-1 肝纤维化 活血化瘀类中药 中医药疗法 Matrix Metalloproteinase-1 Hepatic Fibrosis Tissue Inhibitor of Matrix Metalloproteinase-1 Blood-activating and Stasis-eliminating Drugs
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