低剂量促红细胞生成素减轻急性肾损伤后的慢性纤维化病变

Low-dose erythropoietin alleviates the chronic fibrosis of kidney in mice models of renal ischemiareperfusion injury

目的探讨低剂量促红细胞生成素（EPO）减轻肾缺血性损伤后间质纤维化的作用及其机制。方法通过单侧肾缺血再灌注损伤模型造成小鼠患侧肾间质纤维化，小鼠随机分为假手术组、模型组和低剂量EPO给药组，术后28d处死各组小鼠，取患侧肾做病理学检查，并检测肾组织中层粘连蛋白（LN）、纤维粘连蛋白（FN）、转化生长因子-βl（TGF-131）的水平。结果给药组肾间质纤维化与模型组比较有所减轻；模型组LN、FN、TGF—β1升高（4．39±0．54、4．99±0．22、4．33±0．29、0．91±0．04），EPO给药组明显减低（3．60±0．46、3．85±0．44、3．44±0．52、0．77±0．05），两组间差异有统计学意义（P〈0．01）。结论低剂量EPO可以通过影响TGF—βl表达、抑制细胞细胞传导过程以减轻细胞外基质的积聚。从而减轻间质纤维化．发挥肾保护作用。

Objective To evaluate the possible mechanism of low-dose erythropoietin （EPO） alle- viating renal interstitial fibrosis after ischemia-reperfusion injury （IRI）. Methods Renal interstitial fibro- sis was induced by unilateral renal IRI in mice. Mice were randomly divided into three groups： sham-oper- ated, ischemic control and low-dose EPO treatment. They were sacrificed at 28th day after operation. The kidneys were taken for pathological analysis. The expression of laminin （LN）, fibronectin （FN） and trans- forming growth factor-β1 （TGF-[31） in the kidneys was detected by using immunohistochemistry, and TGF-131 by Western blotting. Results There was remarkable renal interstitial fibrosis in the control group as compared to the EPO group. The levels of LN, FN, and TGF-β1 mRNA and protein were significantly reduced in the EPO group （3. 60±0. 46, 3.85±0. 44, 3.44 ± 0. 52, 0. 77± 0. 05） compared to the con- trol group （4.39±0.54, 4.99±0.22, 4.33±0.29, 0.91±0.04）. Conclusion The results suggested low-dose EPO can reduce the accumulation of extracellular matrix through regulating TGF-β1 expression, thereby alleviating renal interstitial fibrosis and protecting the kidney.