低密度脂蛋白受体相关蛋白在肾间质纤维化模型中的表达

目的:探讨低密度脂蛋白受体相关蛋白在肾间质纤维化中的表达变化及意义。方法:雄性Wistar大鼠随机分为假手术组,模型3、6、9、12d组和血管紧张素转换酶抑制剂(依那普利)治疗9d组。Masson染色结合半定量评分测小管-间质损伤指数,免疫组化确定低密度脂蛋白受体相关蛋白在肾脏的表达部位;蛋白印迹分析检测肾组织内结缔组织生长因子,低密度脂蛋白受体相关蛋白水平。结果:低密度脂蛋白受体相关蛋白阳性表达主要在肾间质和肾小球系膜区中,在单侧输尿管梗阻模型中随观察时间延长逐渐增加,于第9d达高峰;并且第9d依那普利治疗组大鼠肾内低密度脂蛋白受体相关蛋白水平显著少于模型组(P<0.01);相关分析显示,在模型组中低密度脂蛋白受体相关蛋白和结缔组织生长因子蛋白水平呈正相关(r=0.786,P<0.01);低密度脂蛋白受体相关蛋白水平与肾小管间质损伤指数呈正相关(r=0.800,P<0.01)。结论:低密度脂蛋白受体相关蛋白作为结缔组织生长因子的受体蛋白,在大鼠肾间质纤维化模型中表达增加,可能参与肾间质纤维化过程。

Expression of low density lipoprotein receptor-related protein in renal interstitial fibrosis

AIM: To understand the expression of low density lipoprotein receptor-related protein (LRP) in tubulointerstitial fibrosis of unilateral ureter obstruction (UUO) rats. METHODS: The localization of LRP within kidneys were assessed by immunohistochemical staining, the protein level of LRP and connective tissue growth factor (CTGF) in kidney were analysised by Western blot. RESULTS: The location of LRP positive-staining and the protein level of LRP were in the same tendency with CTGF, the level of LRP had strong correlationship with the level of CTGF (r=0.786, P<0.01); The expression of LRP was positive correlated with tubular-interstitial injury index (r=0.800, (P<0.01)). Enalapril treatment downregulated LRP level at 9 days time point. CONCLUSION: The expression of LRP was increased according to the progression of interstitial fibrosis in UUO rats, implicating that LRP may act as receptor of CTGF to mediate the profibrotic effect of CTGF.