红细胞生成素对单侧输尿管梗阻大鼠肾小管上皮-间充质细胞转化的抑制作用及其与VEGF和TSP-1表达变化的关系

目的 探讨红细胞生成素(EPO)对单侧输尿管梗阻(UUO)模型大鼠肾小管上皮-间充质细胞转化的作用,以及这种作用与肾组织血管内皮细胞生长因子(VEGF)和血管形成抑制因子(TSP-1)表达变化的关系.方法 将60只雄性Wistar大鼠分为假手术组(n=20)、UUO对照组(n=20)及EPO治疗组(n=20),分别于手术后第3、7、14、21天处死动物留取肾组织标本.应用免疫组化方法和Western blot方法测定肾组织中α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)、VEGF和TSP-1的表达程度.结果 手术后第3、7天EPO治疗组较UUO对照组α-SMA表达明显减少(P<0.05),E-cadherin表达明显增加(P<0.05).术后第3、7、14天,EPO治疗组TSP-1表达明显低于UUO对照组(P<0.05),而VEGF表达明显高于UUO对照组(P<0.05).结论 EPO具有抑制UUO模型大鼠早期肾小管上皮-间充质细胞转化作用,该作用可能与EPO下调肾组织TSP-1表达,上调VEGF表达有关.

Erythropoietin suppresses epithelial to mesenchymal transition and its possible mechanisms in unilateral uretheral obstruction rats

Objective To examine the effects of erythropoietin（EPO） on epithelial-mesenchymal transition（EMT） in the rat model of unilateral ureteral obstruction and elucidate its possible mechanisms.Methods Sixty male Wistar rats were divided into three groups,sham-operated group（n=20）,UUO group（n=20）,EPO group（n=20）.UUO rats treated with EPO 100 IU/kg,thrice weekly.All the rats were sacrificed at day 3,7,14 and 21.Immunohistochemistry method and Western blot were used to evaluate the extent of expressions of alpha smooth muscle actin（α-SMA）,E-cadherin,vascular endothelial growth factor（VEGF）and thrombospondin-1（TSP-1）.Results The expression of α-SMA were significantly lower in EPO group at day 3 and 7 after UUO operation compared with the UUO group（P0.05）,while E-cadherin expression were significantly higher in EPO group at day 3 and 7（P0.05）.The expressions of TSP-1 were significantly lower in EPO group than that in the UUO rats at day 3,7 and 14（P0.05）,respectively.Meanwhile VEGF expression was significantly higher in EPO group than that in the UUO rats at day 3,7 and 14（P0.05）.Conclusions EPO may ameliorate EMT in rat model of obstructive nephropathy while preventing loss of VEGF and inhibiting TSP-1.The exact mechanism needs to be studied further.