基质细胞衍生因子-1/趋化因子受体4轴在促红细胞生成素动员骨髓间充质干细胞治疗脊髓损伤中的作用  

Effect of stromal cell derived factor-1/CXC chemokine receptor axis in the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward the sites of injured spinal cord

作　　者：郭卫春[1] 李军[1] 熊敏[2] 余化龙[2] 曾云[2] 唐冰[1] 

机构地区：[1]武汉大学人民医院骨科,430060 [2]湖北医药学院附属东风医院骨科研究所

出　　处：《中华实验外科杂志》2015年第7期1506-1509,共4页Chinese Journal of Experimental Surgery

基　　金：湖北省科技厅指导项目（2013CFC035）

摘　　要：目的 观察基质细胞衍生因子-1/趋化因子受体4（SDF-1/CXCR4）轴在促红细胞生成素（EPO）动员骨髓间充质干细胞（BMSCs）治疗大鼠脊髓损伤中的作用.方法 将96只成年雌性SD大鼠随机分为假手术组、模型对照组、EPO组、BMSCs组、BMSCs＋ EPO组和BMSCs＋ EPO＋AMD3100组,每组16只,采用改良Allen法制作大鼠脊髓损伤模型,通过Basso-Beattie-Bresnahan （BBB）评分估计神经功能恢复情况,通过酶联免疫吸附试验（ELISA）法测定脊髓损伤后肿瘤坏死因子（TNF-α）和SDF-1水平,应用免疫荧光检测损伤的脊髓中BMSCs的分布,通过Transwell实验探索EPO对BMSCs迁移功能的影响,原位缺口末端标记法（TUNEL）法检测各组凋亡指数,Western blot检测损伤局部促红细胞生成素受体（EPOR）和CXCR4的水平.结果 术后第7天各组BBB评分分别为：（20.7±3.4）、（6.4±1.7）、（9.5±2.7）、（9.9±1.9）、（11.4±3.6）、（7.0±1.2）分;术后第28天各组BBB评分分别为：（21.0±3.8）、（10.5±2.8）、（15.3±3.6）、（16.2±3.9）、（18.5±4.0）、（10.8±2.2）分,BMSCs＋ EPO组运动功能改善显著优于其他各组（P＜0.05）,EPO能够显著降低受损脊髓中TNF-α水平并上调SDF-1水平（P＜0.05）,EPO较对照组能显著促进BMSCs的迁移（P＜0.05）.结论 EPO可以通过上调SDF-1/CXCR4轴的表达动员骨髓基质干细胞向脊髓损伤部位迁移,并促进BMSCs对脊髓损伤的修复作用.Objective To investigate the effect of stromal cell derived factor-1/CXC chemokine receptor （SDF-1/CXCR4） axis in the migration of transplanted bone marrow mesenchymal stem cells （BMSCs） mobilized by erythropoietin （EPO） toward the spinal cord injury （SCI） sites.Methods Sixty adult female SD rats were randomly divided into sham operation group,model control group,EPO group,BMSCs ＋ EPO group and BMSCs ＋ EPO ＋ AMD3100 group.The SCI model was created using a modified Allen method.Basso-Beattie-Bresnahan （BBB） scale was used to estimate the neurological recovery after SCI.Enzyme linked immunosorbent assay （ELISA） was applied to detect the tumor necrosis factor-α （TNF-α） and SDF-1 levels.Immunofluorescent assay was carried out to identify the distribution of BMSCs in the injured spinal cord.Transwell mnigration assay was performed to detect BMSCs migration.TdT-mediated dUTP nick end labeling （TUNEL） assay was done to detect the apoptosis index.Western blotting was used to assess the expression of erythropoietin receptor （EPOR） and CXCR4.Results BBB scores in sham operation group,model control group,EPO group,BMSCs ＋ EPO group and BMSCs ＋ EPO ＋ AMD 3100 group were 20.7 ± 3.4,6.4 ± 1.7,9.5 ± 2.7,9.9 ± 1.9,11.4 ± 3.6 and 7.0 ± 1.2 seperatelyon the 7th day post-injury,and 21.0 ±3.8,10.5 ±2.8,15.3 ± 3.6,16.2 ±3.9,18.5 ±4.0 and 10.8 ±2.2 seperately on the 28th day post-injury,suggesting the improvement of motor function in the BMSCs ＋ EPO group was more significant than other groups （P ＜ 0.05）.EPO could significantly decrease TNF-α level and increase SDF-1 level in the injured spinal cord （P ＜0.05）,and promoted the migration of BMSCs （P ＜ 0.05）.Conclusion EPO could mobilize BMSCs to the SCI site and promote the anti-apoptosis function of the BMSCs by up-regulating the expression of SDF-1/CXCR4 axis.

关 键 词：基质细胞衍生因子-1/趋化因子受体4轴 骨髓间充质干细胞 红细胞生成素 脊髓损伤 

分 类 号：R977.1[医药卫生—药品]