红细胞生成素对单侧输尿管梗阻大鼠肾间质纤维化的作用及对MCP-1和TGF-β1表达的影响

The effects of erythropoietin on renal interstitial fibrosis and on the expression of MCP-1 and TGF-β1 in unilat-eral ureteral obstruction rats

目的探讨红细胞生成素(erythropoietin,EPO)对单侧输尿管梗阻(unilateral ureteralobstruction,UUO)模型大鼠肾间质纤维化的作用及其对单核细胞趋化蛋白1(monocyte chemoattractant pro-tein-1,MCP-1)和转化生长因子β1(transforming growth factor-β1,TGF-β1)表达的影响。方法将60只雄性Wistar大鼠分为假手术组(20例),UUO对照组(20例)及EPO治疗组(20例),分别于手术后第3,7,14,21d处死动物留取肾组织标本。应用马松染色进行肾间质纤维化程度评分;应用免疫组化方法和Western blot方法测定肾组织中MCP-1、TGF-β1的表达程度。结果马松染色显示手术后第3,7d,EPO治疗组肾间质纤维化程度较UUO对照组明显减轻(P<0.05)。手术后第3,7,14d,EPO治疗组MCP-1、TGF-β1的表达明显低于UUO对照组(P<0.05)。结论 EPO可以减轻UUO模型大鼠早期肾间质纤维化程度,该作用可能与EPO抑制肾组织MCP-1和TGF-β1的表达有关。

Objective To examine the effect and to explore the mechanism of EPO on renal interstitial fibrosis in the rat model of unilateral ureteral obstruction. Methods Sixty male Wistar rats were divided into sham-operation group （n=20）, unilateral ureteral obstruction （UUO） group （n=20）, and EPO group （n=20） in which UUO rats were treated with EPO 100IU/kg three times a week. Rats were sacrificed at day 3, 7, 14 or 21 after the treatment. The extent of renal interstitial fibrosis was evaluated by Masson staining of the renal tissue. Immunohistological method and western blot were used to estimate the expression of transforming growth factor--β1 （TGF-β1）, and monocyte chemoattractant protein-1 （MCP-1）. Results The extent of interstitial fibrosis was significantly lower in EPO group at day 3 and 7 after the operation, compared with that in UUO group （P〈0.05）. The expression of MCP-1 and TGF--β1 in renal tissue was significantly lower in EPO group than that in UUO group at day 3, 7 and 14, respectively （P〈0.05）. Conclusions EPO may reduce the extent of renal fibrosis in the rat UUO model. This effect may relate to the downregulation of TGF-β1 and MCP-1 expression, but the exact mechanism needs to be further studied.