The Role of SDF-1α/CXCR4 Signal Pathway in the Therapeutic Effects of Hypoxic Preconditioning of Endothelial Progenitor Cell Transplantation on Ischemia Heart Disease / 天津医药

ABSTRACT

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 groupscontrol 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.