Objective To investigate the role of stromal cell-derived factor-1α(SDF-1α)/CXCR4 signal pathway in the therapeutic effects of hypoxic preconditioning endothelial progenitor cell (HEPC) transplantation on acute myocardial in-farction Methods Bone marrow endothelial progenitor cells (EPCs) were isolated from syngeneic adult male Wistar rats. EPCs were cultured under normoxic condition for 4 days and 1%O2+5%CO2+94%N2 condition for 3 days. The effect of HEP-Cs on the migration ability of 100μg/L SDF-1αwas observed. Western blot assay was used to detect the expression of CX-CR4, the solo receptor of SDF-1α on cells surface. Then, 26 syngeneic adult male Wistar rats were randomized into 3 groups:control group (n=8),EPCs group (n=9) and HEPCs group (n=9). The acute myocardium infarction animal model was established. At infarction, the rats received 5-points peri-infarct intramyocardial injections of PBS 200μL, 2×106 EPCs and 2 × 106 HEPCs. After 4 weeks, the haemodynamics parameters of cardiac function were analyzed by echocardiography. Results Compare with EPCs, the migration ability of HEPCs towards SDF-1α was increased significantly. The result of Western blot analysis showed an increased CXCR4 expression on the cell surface. After 4 weeks of transplantation, the left ventricular end systolic diameter and ejection fraction (EF%) were much improved in HEPCs group than those of EPCs group and control group (P<0.05). Compare with control group, the left ventricular end-diastolic diameter was significantly im-proved in EPCs and HEPCs groups (P<0.05). There was no significant difference in the improvement of the left ventricular end-diastolic diameter between HEPCs and EPCs groups (P>0.05). Conclusion SDF-1α/CXCR4 pathway was up-regu-lated by HEPCs, which showed the therapeutic effects via EPCs. The adjustment of SDF-1α/CXCR4 signaling pathway is an effective method for the treatment of ischemic heart diseases.%目的探讨基质细胞衍生因子-1α（SDF-1α）/CXCR4信号通路在缺氧培养骨髓内皮祖细胞（HEPCs）心肌内移植治疗缺血性心脏病中的生物学效应。方法从同种系成年雄性Wistar大鼠长骨中获取骨髓内皮祖细胞（EPCs）,常规培养4 d后，1%O2+5%CO2+94%N2培养3 d。观察HEPCs对细胞因子100μg/L SDF-1α的迁移能力变化，蛋白印迹法观察HEPCs表面SDF-1α受体CXCR4表达。将同种系成年雄性Wistar大鼠26只，随机分为对照组（n=8），常规组（n=9）和缺氧组（n=9),建立急性心肌梗死模型，在心肌梗死边缘5个不同区域心肌内分别注射PBS溶液200μL，EPCs 2×106个，HEPCs 2×106个，4周后用心脏超声分析血流动力学和心脏功能变化。结果 HEPCs与EPCs相比，细胞对SDF-1α迁移能力明显增强，细胞表面SDF-1α受体CXCR4表达增加。HEPCs心肌内移植4周后心脏超声示,与常规组和对照组比较,缺氧组左室收缩末期内径和射血分数得到明显改善（均P<0.05）；与对照组比较，缺氧组和常规组左室舒张末期内径明显改善（均P<0.05）；而缺氧组和常规组左室舒张末期内径比较，改善不明显（P>0.05）。结论 HEPCs上调细胞表面CXCR4，通过SDF-1α/CXCR4信号通路介导EPCs增强发挥细胞生物学功效。调节SDF-1α/CXCR4信号通路是优化EPCs移植治疗缺血性心脏病的有效方法。
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