Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Am J Nephrol. 2012;35(6):531-9. doi: 10.1159/000339167. Epub 2012 May 30.
Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI.
Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes.
Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly.
These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.
最近人们对骨髓来源的干细胞的可能作用以及促红细胞生成素在缺血性急性肾损伤（AKI）恢复中的治疗作用产生了兴趣。本研究的目的是比较间充质干细胞（MSCs）治疗、达贝泊汀-α（DPO）治疗和两者联合治疗在缺血/再灌注（I/R）AKI 大鼠模型中的效果。
共纳入 40 只雄性 Sprague-Dawley 大鼠，其中 28 只随机分为对照组（用生理血清治疗）或 3 个治疗组中的 1 组，这 3 个治疗组分别用 DPO、MSCs 或两者联合（MSCs 和 DPO 同时治疗）治疗，然后诱导 I/R 损伤。在手术 0、24、48 和 72 h 时采集红细胞比容、血清肌酐和 BUN 水平，并在肾切除后 72 h 时采集肾组织进行组织学分析。使用光镜和电子显微镜，通过标准化的组织学评分系统对组织损伤进行定量评估。
与对照组相比，MSCs 或 DPO 治疗均可改善肾功能，但 MSC/DPO 组的肾功能改善优于其他组。组织学分析表明，与对照组相比，MSCs 或 DPO 组的大鼠组织损伤明显减少，但 MSC 和 DPO 同时治疗的大鼠恢复最好。
这些结果表明，DPO 和 MSCs 的联合应用可能是缺血性肾损伤患者的一种潜在新型肾脏保护治疗方法。
