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
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国家自然科学基金(30570725)


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

    Abstract:

    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.

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余兰,瞿志玲,余俊,张鹏,阮秋蓉.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[J].中国动脉硬化杂志,2010,18(10):757~760.

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  • 收稿日期:2010-08-26
  • 最后修改日期:2010-09-26
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