血浆凝血酶敏感蛋白-1在肾间质纤维化中的表达

Expression of plasma thrombospondin-1 in renal interstitial fibrosis

目的:观察不同时间点血浆凝血酶敏感蛋白-1(TSP-1)在蛋白超负荷肾病大鼠中的表达,分析其与肾小管间质纤维化的关系。方法:45只雄性SD大鼠右肾切除后,随机分成牛血清蛋白(BSA)组和对照组,BSA组大鼠予以腹腔注射牛血清白蛋白,对照组注射生理盐水。分别在第1,5,9周末,检测血常规及生化指标,各时相尿蛋白定量;肾组织行光镜、免疫荧光及电镜检查。采用免疫印迹法检测血浆TSP-1蛋白表达。分析血浆TSP-1表达与肾小管间质病理损害积分之间的相关性。结果:BSA组大鼠24 h尿蛋白定量和肾功能均较对照组有明显差异;肾小管间质病理积分和肾小球硬化指数明显增高;IgG荧光强度明显高于对照组;与对照组比较,BSA组大鼠血浆TSP-1蛋白均明显增高。BSA组血浆TSP-1的蛋白表达水平与肾小管间质病理积分呈正相关(r=0.836,P<0.01)。结论:血浆TSP-1与肾间质纤维化呈正相关,血浆TSP-1可能是临床判断肾间质纤维化程度的重要指标。

Objective To observe the expression of plasma thrombospondin-1（TSP-1） at different time in protein-overload rats and to analyze the relationship between plasma TSP-1 expression and renal interstitial fibrosis.Methods Forty-five male Sprague-Dawley rats were randomly divided into a bovine serum albumin（BSA） group and a control group after uninephrectomization.Rats with protein overload nephropathy induced by intraperitoneally injected BSA were used as a model（control group received saline）.At the 1st,5th,and 9th weekend,the level of 24 h proteinuria and renal function was assessed.Pathological changes were observed by electron and fluorescent microscopy.The expression of plasma TSP-1 was detected by Western blot.The relationship between plasma TSP-1 and tubulointerstitial lesions（TIL） score was analyzed.Results Twenty-four hour proteinuria and blood urea nitrogen（BUN） significantly increased in protein-overload rats compared with those in the control group.While protein-overload rats developed more severe fibrosis in the tubular and interstitium.Glomerulosclerosis index and TIL score were upregulated compared with those in the control group.The expression of TSP-1 increased significantly at the 5th and 9th weekend.The expression of TSP-1 was positively correlated with TIL score（r=0.836,P0.01）.Conclusion Plasma TSP-1 expression is positively correlated with renal interstitial fibrosis in protein-overload rats.Plasma TSP-1 may be used for an important biomarker of renal interstitial fibrosis.