干细胞因子和粒细胞集落刺激因子动员自身骨髓干细胞治疗缺血再灌注肾损伤

背景：骨髓干细胞可分化为肾脏组织固有细胞、修复损伤肾组织。正常情况下,外周血干细胞数目较少,骨髓干细胞动员剂可提高外周血干细胞数目。目的：观察动员自身骨髓干细胞对缺血再灌注损伤肾脏修复作用及对缺氧诱导因子1α系统的影响,分析骨髓干细胞修复损伤肾脏的机制。方法：SD大鼠随机分为4组。对照组不作处置;模型组制备肾缺血再灌注模型;治疗组给予缺血再灌注模型大鼠皮下注射骨髓干细胞动员剂干细胞因子200μg/（kg·d）及粒细胞集落刺激因子50μg/（kg·d）,治疗对照组给予正常大鼠皮下注射与治疗组相同的药物,连续5d。于术后5,10,17,24,31d观察大鼠肾脏病理改变、骨髓干细胞表面抗原标记CD34＋细胞表达以及缺氧诱导因子1α、血管内皮生长因子、血红素加氧酶1的表达变化。结果与结论：①联合应用骨髓干细胞动员剂能明显增加损伤肾组织骨髓干细胞的数量,减轻肾组织损伤程度。②骨髓干细胞能促进肾组织缺氧诱导因子1α系统的表达,缺氧诱导因子1α系统及其靶基因产物血管内皮生长因子、血红素加氧酶1表达增加是骨髓干细胞促进急性肾损伤修复的可能机制之一。③骨髓干细胞动员剂对缺氧诱导因子1α系统的表达有一定的增强作用。

Bone marrow stem cell mobilization with stem cell factor and granulocyte colony-stimulating factor for treatment of renal ischemia/reperfusion injury

BACKGROUND：Bone marrow mesenchymal stem cells（BMSCs） can differentiate into the native cells of renal tissue to repair the injured renal tissue.Under normal circumstance,peripheral blood stem cells are limited in number,and mobilization of BMSCs can increase the number of peripheral blood stem cells.OBJECTIVE：To observe the therapeutic effects of BMSC mobilization on repair of ischemia/reperfusion-induced renal injury and on hypoxia inducible factor-1a and to investigate the mechanism by which BMSC mobilization repairs renal injury.METHODS：Sprague-Dawley rats were randomly allocated into four groups：In the control group,there was no treatment.In the model group,renal ischemia/reperfusion model was prepared.In the treatment group,200 μg/kg per day stem cells and 50 μg/kg per day granulocyte colony-stimulating factors were subcutaneously administered in rat models of ischemia/reperfusion renal injury to mobilize BMSCs.In the treatment control group,normal rats received the same administration as rats in the treatment group.Drug administration was performed for a total of 5 successive days.At 5,10,17,24,31 days post-surgery,renal tissue was resected for pathological observation,and the expression level of CD34＋ cells,hypoxia inducible factor-1a,vascular endothelial growth factor and heme oxygenase 1 was detected.RESULTS AND CONCLUSION：Application of stem cell factors combined with granulocyte colony-stimulating factors could significantly increase BMSCs in the injured renal tissue and alleviate the injury degree of renal tissue.BMSCs can increase hypoxia inducible factor-1a expression,vascular endothelial growth factor and heme oxygenase 1,which may be one of possible mechanisms by which BMSCs promote the repair of acute renal injury.BMSC mobilization can promote the expression of hypoxia inducible factor-1a system.