大黄素对肾纤维化大鼠肾组织中基质金属蛋白酶组织抑制物-1表达的影响

The effect of emodin on expression of tissue inhibitor of metalloproteinase-1 in rat with renal tubulointerstitial fibrosis

目的探讨中药大黄素对肾间质纤维化模型大鼠肾组织中基质金属蛋白酶组织抑制物-1(TIMP-1)表达的影响。方法 160只Wister大鼠随机分成四组:正常对照组、假手术组、模型组及大黄素治疗组。制备单侧输尿管梗阻(UUO)模型。治疗组在UUO的基础上每天以大黄素40mg/kg灌胃,采用病理及免疫组化的方法动态观察各组大鼠术后d1、d3、d7、d14梗阻侧肾脏的组织学变化和TIMP-1在梗阻肾小管间质中表达情况。结果模型组TIMP-1的表达持续增加;治疗组TIMP-1的表达水平低于模型组(P<0.01)。结论中药大黄素可以通过抑制TIMP-1的表达来发挥其延缓肾间质纤维化进程的作用,对肾脏有保护作用。

Objective To investigate the dynamic changes of TIMP-1 expressions in renal interstitial fibrosis（RIF）,and to explore the mechanism of RIF and the effect of emodin. Methods One hundred and sixty rats were randomly divided into 4 groups：the normal control group,the sham-operated group,the UUO group and the emodin treated group（DTG）. Rat in the DTG were administered intragastrically with emodin 40mg/kg daily after modeling.Ten rats of each group were sacrificed respectively at 1,3,7 and 14 days after UUO. Renal histopathological changes was observed by light microscope.The expression of TIMP-1 was examined by immunohistochemistry at each time point.Results In UUO group,the express of TIMP-1 in renal interstitium was increased gradually. In DTG group,the express of TIMP-1 decreased significantly compared to the same time in the UUO group（P〈0.01）.Conclusions Emodin can delay the progression of renal tubulointerstitial fibrosis and protect the function of renal tubule probably by inhibiting the expression of TIMP-1.