sEHi对冠心病患者内皮祖细胞功能的影响

Effect of soluble epoxide hydrolase inhibitor on the function of endothelial progenitor cells in patients with coronary heart disease

目的:观察可溶性环氧化物水解酶抑制剂(soluble epoxide hydrolase inhibitor,sEHi)tAUCB对冠心病(CHD)患者外周血来源的内皮祖细胞(endothelial progenitor cells,EPCs)迁移、血管生成能力和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法:采用密度梯度离心法从CHD患者外周血获取单个核细胞培养7 d后,采用免疫荧光和流式细胞仪进行EPCs的鉴定;随后用不同浓度(0,10-6,10-5,10-4mol/L)tAUCB干预24 h,分别用Transwell小室和Matrigel-Matrix管腔形成的体外模型检测其迁移、血管生成能力的变化,提取蛋白用Western印迹检测EPCs VEGF的表达。培养年龄性别匹配的健康对照者的EPCs作为对照组。结果:与健康对照组相比,CHD患者EPCs的迁移及血管生成能力均显著下降(P<0.05);与处理前(0 mol/L tAUCB)相比,tAUCB呈浓度依赖性地显著增加CHD患者EPCs迁移、血管生成能力并促进CHD患者EPCs表达VEGF。10-6mol/L tAUCB即明显增加CHD患者EPCs的上述功能并促进其VEGF的表达(P<0.05)。结论:sEHi具有正向调节CHD患者EPCs功能的作用,其有望成为一类治疗CHD的新型药物。

Objective To investigate the effect of soluble epoxide hydrolase inhibitor（sEHi） tAUCB on the function of endothelial progenitor cells（EPCs） and expression of vascular endothelial growth factor（VEGF） in EPCs in patients with coronary heart disease（CHD）.Methods Mononuclear cells,from the peripheral blood of CHD patients,were isolated by ficoll density gradient centri-fugation and cultured.After 7 days of culture in vitro,EPCs were identified by double staining and flow cytometry.EPCs were then stimulated by 0,10-6,10-5,and 10-4 mol/L of tAUCB for 24 h.Migration assay was performed in transwell chamber and tube formation assay was performed by Matrigel-Matrix in vitro model.The expression of VEGF in EPCs was measured by Western blot.EPCs from age and gender matched healthy subjects were also cultured as controls.Results The migration and tube formation activities of EPCs from CHD patients were obviously damaged compared with those from healthy controls（P0.05）.The tAUCB could dose-dependently increase the migration and tube formation activities and increase the expression of VEGF in EPCs compared with those from CHD patients without treatment.The 10-6 mol/L tAUCB increased those activities of EPCs and the expression of VEGF with statistical difference.Conclusion sEHi can positively modulate the function of EPCs from CHD patients,suggesting the potential predictive significance of sEHi in the therapy of CHD.