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

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 investigate the relationship between the expression of TIMP - 1 in kidney and the pathogenesis of membranous nephropathy (MN). Methods: Mice were randomly divided into model group and control group. Animals in model group were injected with cationic bovine serum albumin (C-BSA) every other day for MN model and control group were injected normal saline as negative control. Urinary protein qualitative test since the third week. All rabbits were sacrificed at the end of the 4th week, immunofluorescence was performed in kidney tissues, and the morphological changes were observed by light microscope and electron microscope. The expression of TIMP - 1 in renal tissues was detected by immunohistochemistry (SABC method) Semi-quantitative observation; image analysis system to detect basement membrane (BM) thickness. Results: Model group model was established successfully. The expression of TIMP - 1 in the kidney of the model group and the control group was mainly expressed in the cytoplasm of renal tubular epithelial cells. The expression of TIMP - 1 was only sporadic in the glomerular cells of the model group, but not in the control group. 1 expression. The expression of TIMP - 1 in model group was significantly higher than that in control group (P <0.01). The glomerular basement membrane (GBM) and tubule basement membrane (TBM) (P <0. 01). Statistical analysis showed that there was a positive correlation between the expression of TIMP - 1 and the thickness of GBM (0. 01

0.05). Conclusion: The increased expression of TIMP - 1 is positively correlated with the thickening of GBM and TBM, suggesting that elevated TIMP - 1 is involved in the mechanism of thickening of GBM and TBM and plays an important role in the pathogenesis of MN.