CD47在单侧输尿管梗阻大鼠模型中调控血管生成的作用研究

The angiogenesis regulation function of CD47 on unilateral ureteral obstruction

目的探讨整合素相关蛋白CD47在单侧输尿管梗阻(UUO)大鼠模型中对血管调控的作用。方法将SD大鼠随机分为2组:UUO组50只和假手术组(SOR)25只。UUO组随机选取10只分别于术后3、7、14、21和28天处死,;SOR组随机选取5只于按相同时间点处死。行HE染色观察肾间质病理学改变;免疫组化技术观察CD34、VEGF、TSP-1、CD47的表达。结果 UUO组呈进行性肾间质纤维化改变,包括小管的萎缩、扩张、炎细胞浸润以及CD34、VEGF表达下降(P<0.05);肾小管损伤评分、TSP-1、CD47的表达水平升高(P<0.05)。相关分析显示CD47的表达与CD34的表达呈负相关(r=-0.925,P<0.01),与VEGF表达也呈负相关(r=-0.946,P<0.01)。结论 CD47与其配体TSP-1结合,可能通过调控内皮细胞VEGF信号的传导,参与UUO大鼠模型RIF过程中血管病变的发生发展。

Objective To prove the angiogenesis regulation function of CD47,a kind of IAP,in unilateral ureteral obstruction.Methods Sprague-Dawley rats were randomly divided into 2groups：UUO group（UUO）（n=50,shamoperation group（SOR）（n=25）,and randomly sacrificed the same amount at 3,7,14,21 and 28days after UUO or sham-operation.The histological changes of renal interstitial tissues were observed by HE and the protein of CD34,VEGF,Tsp-1and CD47 expression was assessed by immunohistochemistry.Results In UUO model,the obstructed kidney showed typical features of renal tubulointerstitial fibrosis,such as severe tubular loss,dilation,atrophy,infiltration of inflammatory cells（P0.05）.The expression of CD34 and VEGF were decreased.TIS,the score of renal interstitial lesion and the expression of TSP-1and CD47 were significantly higher in UUO group than SOR.The expression of CD47 was negative correlation with the expression of CD34（r=-0.925,P0.01）and the expression of VEGF（r=-0.946,P0.01）.Conclusion CD47,a receptor for TSP-1,may be,through blinding tsp-1to limit VEGF-mediated effects on vascular cells,played a role of angiogenesis regulation on renal interstitial fibrosis with unilateral ureteral obstruction.