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目的探讨红细胞生成素对单侧输尿管梗阻大鼠肾脏纤维化的影响及其机制。方法建立单侧输尿管梗阻大鼠模型,并把实验动物分成假手术组(对照组)、单侧输尿管梗阻组、单侧输尿管梗阻大鼠红细胞生成素小剂量治疗组(100 u.kg-1.d-1红细胞生成素,小剂量组)和单侧输尿管梗阻大鼠红细胞生成素大剂量治疗组(1 000 u.kg-1.d-1红细胞生成素,大剂量组)。在单侧输尿管梗阻术后第3～14天隔天腹膜内注射红细胞生成素,所有大鼠在第14天处死;观察肾组织病理变化;免疫组化检测各组大鼠肾组织α-平滑肌肌动蛋白、上皮细胞钙黏蛋白和补体C3的表达。结果与单侧输尿管梗阻组比较,单侧输尿管梗阻大鼠用红细胞生成素治疗后,梗阻侧肾脏胶原纤维含量明显减少,且大剂量红细胞生成素治疗组减少更明显。与对照组比较,单侧输尿管梗阻组大鼠梗阻侧肾脏肾小管上皮细胞α-平滑肌肌动蛋白大量表达,肾小管上皮细胞钙黏蛋白表达明显减弱,并可见肾小管上皮细胞大量表达C3。与单侧输尿管梗阻组比较,单侧输尿管梗阻大鼠用红细胞生成素治疗后,梗阻侧肾脏肾小管上皮细胞C3和α-平滑肌肌动蛋白表达明显减弱,上皮细胞钙黏蛋白表达明显增强,以上改变在大剂量红细胞生成素治疗组更加明显。结论红细胞生成素可抑制单侧输尿管梗阻大鼠肾小管上皮间充质转分化,减轻肾间质纤维化,这种作用可能与其抑制肾小管上皮细胞补体C3的表达有关。
Objective To investigate the effect of erythropoietin on renal fibrosis in rats with unilateral ureteral obstruction and its mechanism. Methods The rat model of unilateral ureteral obstruction was established. The experimental animals were divided into sham operation group (control group), unilateral ureteral obstruction group and unilateral ureteral obstruction rat erythropoietin small dose treatment group (100 u.kg-1. d-1 erythropoietin, low-dose group) and high-dose erythropoietin treatment group (1 000 u.kg-1.d-1 erythropoietin, high-dose group) with unilateral ureteral obstruction. All rats were sacrificed on the 14th day after intraperitoneal injection of erythropoietin on the third day to the 14th day after unilateral ureteral obstruction. The pathological changes of renal tissues were observed. The expressions of α-smooth muscle Actin, E-cadherin, and complement C3 expression. Results Compared with unilateral ureteral obstruction group, unilateral ureteral obstruction in rats with erythropoietin treatment, obstructive renal collagen fibers decreased significantly, and high-dose erythropoietin treatment group decreased more significantly. Compared with the control group, unilateral ureteral obstruction group renal tubulointerstitial α-smooth muscle actin expression in large numbers, renal tubular epithelial cell cadherin expression was significantly reduced, and the large tubular epithelial cells express C3. Compared with unilateral ureteral obstruction group, unilateral ureteral obstruction in rats with erythropoietin treatment, obstructive renal tubular epithelial cells C3 and α-smooth muscle actin expression was significantly reduced, the expression of E-cadherin increased significantly, the above Changes were more pronounced in the high-dose erythropoietin-treated group. Conclusion Erythropoietin can inhibit renal tubular epithelial mesenchymal transdifferentiation and renal interstitial fibrosis in unilateral ureteral obstruction rats. This effect may be related to the inhibition of complement C3 expression in renal tubular epithelial cells.