促红细胞生成素干预对骨髓间充质干细胞移植修复小鼠急性肾损伤的作用机制

肾脏病与透析肾移植杂志 ›› 2012, Vol. 21 ›› Issue (5): 444-449.

促红细胞生成素干预对骨髓间充质干细胞移植修复小鼠急性肾损伤的作用机制

出版日期:2012-10-24 发布日期:2012-10-24

EPO Intervention on Controlling of Acute Kidney Injury Repair by Bone Marrow Mesenchymal Stem Cells Transplantation for Mice

Online:2012-10-24 Published:2012-10-24

摘要/Abstract

摘要：

摘要目的:构建缺血再灌注（I/R）诱导的急性肾损伤（AKI）小鼠模型，经尾静脉注射行骨髓间充质干细胞（BM-MSCs）移植，观察外源性促红细胞生成素（EPO）对BM-MSCs移植修复AKI效应的调控，并探讨基质细胞衍生因子1（SDF-1）/CXCR4轴在调控中所起的作用。方法:C57BL/6小鼠100只，随机分为正常对照组、模型组（AKI组）、BM-MSCs移植组、EPO干预组、EPO干预+BM-MSCs移植组，移植BM-MSCs采用5-溴脱氧尿嘧啶核苷（BrdU）标记。于建模后1d、3d、7d、14d处死部分小鼠，检测血尿素氮（BUN）及肌酐（SCr）水平，观察肾组织病理变化，行肾小管损伤程度评分，免疫组织化学观察移植BM-MSCs在小鼠肾组织的分布，Western印迹法检测损伤肾组织中SDF-1水平。结果:与BM-MSCs移植组及EPO干预组比较，EPO干预+BM-MSCs移植组小鼠BUN、SCr以及ATN评分降低幅度更大，至移植后第14d，小鼠的BUN、SCr水平甚至接近正常对照组。免疫组化显示BM-MSCs移植组小鼠肾脏中可检测到BrdU＋细胞分布，以术后第7天最多（11.32%±1.38%），在此基础上联合EPO干预可增加肾组织中BrdU+阳性细胞比例。AKI建模后肾组织SDF-1水平升高，建模后7d达高峰，EPO干预可显著增加SDF-1的表达。结论：EPO干预可增加BM-MSCs移植后受损肾组织中移植细胞数量，增强AKI的修复作用，其中肾脏中促干细胞归巢因子SDF-1表达增加为其可能机制之一。

关键词: 骨髓间充质干细胞, 急性肾损伤, 促红细胞生成素, 基质细胞衍生因子1

Abstract:

ABSTRACT Objectives: To investigate the effect of exogenous EPO intervention on AKI repair by bone marrow mesenchymal stem cells(BM-MSCs) transplantation, and the role of SDF-1/CXCR4 axle in the effect has also been discussed. Methodology: Altogether one hundred C57BL/6 mice had been randomly divided into five groups. They were normal group (n=20), model group (AKI group, n=20), BM-MSCs transplantation group (n=20), EPO intervention group (n=20), and EPO intervention + BM-MSCs transplantation group (n=20). Transplanted BM-MSCs were marked by BrdU. Some mice had been sacrificed after the model been constructed 1d, 3d, 7d, and 14d respectively; arterial blood was reserved for testing blood BUN and SCr level; pathological changes for renal tissue have been observed and the injury degree for renal tubular has been scored; BM-MSCs distributed in renal tissue for recipient mice were observed with immunohistochemistry method and SDF-1 level in injured renal tissue was tested by Western Blot. Results: Compared with BM-MSCs transplantation group and EPO intervention group, BUN, SCr and ATN scores were declined sharply in EPO internvention + BM-MSCs transplantation group; on the 14th day after the transplantation, BUN, SCr degrees for the mice were even close to that of normal group. IHC showed that BrdU+ cells distribution could be detected in the mice kidneys for BM-MSCs transplantation group, and the value reached to the peak on the 7th day after the surgery （11.3％±1.38％）; EPO intervention combined with BM-MSCs transplantation could increase the number of BrdU+ positive cells in renal tissue. SDF-1 level was raised for renal tissue after AKI model been constructed, which went to the peak on the 7th day after the model been constructed, and SDF-1 expression could be obviously increased with EPO intervention. Conclusions: EPO intervention could increase the number of transplanted cells after BM-MSCs transplantation, enhance AKI repair effect. The high level of SDF-1 expression, which could promote stem cells homing to kidneys, may be one of possible mechanisms.

Key words: bone marrow mesenchymal stem cells, acute kidney injury, erythropoietin, stromal cell derived factor-1

刘楠梅，田军，韩国锋，等 . 促红细胞生成素干预对骨髓间充质干细胞移植修复小鼠急性肾损伤的作用机制[J]. 肾脏病与透析肾移植杂志, 2012, 21(5): 444-449.

Liu Nan-mei, Tian Jun, Han Guo-feng,et al. EPO Intervention on Controlling of Acute Kidney Injury Repair by Bone Marrow Mesenchymal Stem Cells Transplantation for Mice[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, 2012, 21(5): 444-449.

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