促红细胞生成素通过基质细胞衍生因子1α介导小鼠骨髓KDR^+干细胞自体动员以及心肌梗死后的修复作用及其机制  

Erythropoietin Mobilizes the KDR^+ Stem Cells from Mouse Bone Marrow via Stromal Derived Factor-1α and Repair After Myocardial Infarction and Its Mechanism

作　　者：余兰[1] 瞿志玲[1] 余俊[1] 张鹏[1] 阮秋蓉[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院病理研究所,湖北省武汉市430030

出　　处：《中国动脉硬化杂志》2010年第10期757-760,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30570725)

摘　　要：目的探讨促红细胞生成素自体动员骨髓KDR+干细胞对小鼠心肌梗死的修复作用及其相关机制。方法用冷冻法制造小鼠急性心肌梗死模型,造模后随机分为四组:促红细胞生成素组、AMD3100抑制组、阴性对照组和假手术组。最后一次给药后1h流式细胞术检测外周血中KDR+细胞数。分别于造模后2周和4周免疫组织化学法检测心肌梗死边缘区新生毛细血管数。结果流式细胞术检测发现,促红细胞生成素组KDR+细胞数(2.88%±0.67%)较阴性对照组(0.68%±0.24%)及假手术组(0.62%±0.24%)明显增高,而AMD3100抑制组KDR+细胞数(0.28%±0.13%)较促红细胞生成素组明显减少(P<0.05)。免疫组织化学检测发现,造模后2周和4周,促红细胞生成素组心肌梗死边缘区新生毛细血管数较AMD3100抑制组和阴性对照组明显增高(P<0.05),而AMD3100抑制组心肌梗死边缘区新生毛细血管数只在造模后2周较阴性对照组增高(P<0.05)。结论促红细胞生成素能有效动员骨髓KDR+干细胞到外周血中并到达心肌梗死缺血区参与新生毛细血管的形成。这种作用能够被AMD3100完全抑制,提示促红细胞生成素自体动员骨髓KDR+干细胞到外周血可能是通过基质细胞衍生因子1α及其受体CXCR4轴实现的。Aim To study whether erythropoietin（EPO）has effect on bone marrow KDR^＋ stem cells and the possible mechanism in mice with acute myocardial infarction（AMI）.Methods Acute myocardial infarction mice were established by cryoinjury.Sixty male mice were randomly divided into four groups after cryoinjury：EPO group,AMD3100 inhibition group,control group,sham surgery group.The changes of KDR positive cells in peripheral blood were determined by flowcytometry.Immunohistochemisty was used to detect capillary density of peri-infarct area in 2 and 4 weeks after surgery.Results Compared with EPO group,the number of KDR positive cells in peripheral blood decreased in AMD3100 inhibition group（2.88%±0.67% vs 0.28%±0.13%,P〈0.05）.Two and four weeks after acute myocardial infarction modeling,the capillary density in EPO group was significantly higher than that in AMD3100 inhibition group and control group（P〈0.05）.But only 2 weeks after surgery,the capillary density in AMD3100 inhibition group was higher than that in control group（P〈0.05）.Conclusion EPO can effectively mobilize KDR^＋ stem cells from bone marrow to peripheral blood,which increased capillary density in peri-infarct area in mice with acute myocardial infarction.The effect can be completely restrained by AMD3100,which suggested that EPO may mobilize KDR^＋ cells in bone marrow to peripheral blood by SDF-1α/CXCR4 axis.

关 键 词：促红细胞生成素 心肌梗死 KDR^+干细胞 基质细胞衍生因子1Α 

分 类 号：R363[医药卫生—病理学]