小鼠膜性肾病肾脏中TIMP-1的表达及意义

Expression of TIMP-1 Protein in Kidney of Mice with Membranous Nephropaty

目的 :探讨肾脏TIMP - 1的表达与膜性肾病 (MN)发病机制间的关系。方法 :将小鼠随机分为模型组和对照组 ,模型组采用隔日尾静脉注射阳离子化牛血清白蛋白 (C -BSA)复制MN动物模型 ,对照组全程注射生理盐水作为阴性对照。自第 3周起做尿蛋白定性试验。第 4周末全部杀检 ,取肾脏组织做免疫荧光、光镜、电镜定性观察 ,证实模型建立成功 ;用免疫组织化学 (SABC法 )检测肾脏组织中TIMP - 1表达 ,并在光镜下定性、半定量观察 ;用图像分析系统检测基底膜 (BM )厚度。结果 :模型组模型建立成功。模型组和对照组肾脏中均有TIMP - 1表达 ,主要表达在肾小管上皮细胞胞浆中 ,模型组肾小球细胞中TIMP - 1仅有散在表达 ,而对照组肾小球细胞无TIMP - 1表达。模型组肾组织中TIMP - 1表达明显强于对照组 (P <0 .0 1) ;模型组肾小球基底膜 (GBM )和肾小管基底膜 (TBM )较对照组均明显弥漫性增厚 (P <0 .0 1)。统计分析显示 :模型组肾组织中TIMP - 1表达与GBM厚度呈正相关 (0 .0 1<P <0 .0 5 ) ,与TBM厚度呈明显正相关 (P <0 .0 1) ;对照组TIMP - 1表达与GBM和TBM厚度均无相关性 (P >0 .0 5 )。结论 :TIMP - 1表达增高与GBM和TBM增厚呈正相关 ,表明TIMP - 1升高参与了GBM和TBM增厚形成的机制 ,在MN的发病中起着重要作用。

Objective:To research the relativity beween mechanism and TIMP-1 protein expression in mice with membranous nephropathy.Methods:Membranous nephropathy mice animals model were used,and the TIMP-1 protein expression in kidney was assessed by immunohistochemistry and the thickness of GBM and TBM was measured.Then the statistical methods were used to compare and analyse the data of MN group and control group.Results:TIMP-1 protein was expressed mainly in renal tubule of MN group and control group.In glomerulus,a small amount of TIMP-1 was expressed in MN group,and no TIMP-1 was expressed in control group.The level of TIMP-1 protein in MN group increased remarkably comparing with control group.The GBM and TBM in MN group were thicker than those in control group and the GBM and TBM in control group were normal.Then the statistical analyse shows:In MN group,the expression of TIMP-1 protein paralleled with the thickness of GBM and TBM,and In control group,the expression of TIMP-1 protein was not relative to the thickness both of GBM and TBM;Conclusion:The level of TIMP-1 protein expression is positively relative to the thickening of GBM and TBM,and TIMP-1 act an important action during the developing of MN.