红细胞生成素对慢性肾衰竭大鼠肾小球内皮细胞功能的影响

目的 探讨红细胞生成素（EPO）对慢性肾衰竭（CRF）大鼠肾小球内皮细胞功能的影响。 方法 采用分阶段5/6肾切除术制备大鼠慢性肾衰竭动物模型。实验动物按数字随机法分为4组：假手术组（对照组）、慢性肾衰竭组（模型组）及EPO干预的两个剂量组（小剂量组EPO用量30 U/kg，大剂量组EPO用量50 U/kg）。慢性肾衰竭大鼠皮下注射EPO 6周后处死。检测各组大鼠血肌酐（Scr）、血尿素氮（BUN）、尿蛋白、血红蛋白（Hb）和血压的变化，并观察肾组织病理改变。免疫组化法检测肾小球CD34、CD31表达；RT-PCR检测肾组织内皮素1（ET-1）、内皮细胞一氧化氮合酶（eNOS）和血管内皮细胞生长因子（VEGF） mRNA的表达。 结果 与模型组比较，EPO治疗能显著增加大鼠肾小球CD34、CD31的表达（均P < 0.05）；下调肾组织ET-1 mRNA的表达（P < 0.05）；上调肾组织eNOS和 VEGF mRNA的表达（均P < 0.05）。此外，EPO治疗还能使大鼠Scr、BUN、尿蛋白和血压水平显著降低（均P < 0.05），Hb水平显著增高（P < 0.05），肾组织病理损害明显减轻。 结论 EPO能减轻慢性肾衰竭大鼠肾脏的病理损害，改善肾功能。这种作用可能与其促进肾小球内皮细胞的修复和改善内皮功能有关。

Effects of erythropoietin On glomerular endothelial cells function in rats with chronic renal failure

Objective To investigate the effects of erythropoietin (EPO) on the function of glomerular endothelial cells in rats with chronic renal failure (CRF). Methods The CRF model was established by a two stage 5/6 nephrectomy procedure in rats. Experimental rats were randomly divided into four groups: sham operation group (control group), CRF group, CRF rats treated with 30 U/kg EPO (low-dosage group) and with 50 U/kg EPO (high-dosage group). CRF rats received EPO by hypodermic injection for 6 weeks and then were sacrificed. Serum creatinine (Scr), blood urea nitrogen (BUN), urine protein, haematoglobin (Hb) and blood pressure were measured. The renal morphologic changes were evaluated on periodic acid-schiff (PAS) stained sections. The CD34 and CD31 expressions in glomerulus were detected by immunohistochemistry method. The mRNA of endothelin 1(ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor(VEGF) were detected by RT-PCR. Results The expressions of CD34 and CD31 protein in glomerulus, and the expressions of eNOS and VEGF mRNA in renal tissue were higher in EPO treatment group than those in CRF model group (all P<0.05). The expression of ET-1 mRNA in renal tissue was lower in EPO treatment group than that in CRF model group. In addition, the Scr, BUN, urine protein and blood pressure in EPO treatment group were significantly lower than those in CRF model group (all P<0.05). Haematoglobin in EPO treatment group was higher than that in CRF model group (P<0.05). Reanl pathological injury was improved by EPO treatment in dose-dependent manner. Conclusion EPO can ameliorate renal pathological injury and renal function in rats with chronic renal failure, maybe through promoting the renovation of glomerular capillary endothelium and improving the function of glomerular endothelial cells.