拉西地平对原发性高血压患者内皮祖细胞内皮修复能力的影响

Effect of Lacidipine on Re-endothelialization Capacity of Endothelial Progenitor Cells from Hypertensive Patients.

目的探讨拉西地平对高血压患者外周血内皮祖细胞(EPCs)体外功能活性及在体再内皮化能力的影响。方法选择初发的原发性高血压患者和性别、年龄匹配的健康志愿者各10例,分离其外周血单个核细胞诱导分化成EPCs。培养7天后用不同浓度的拉西地平10、100以及1000nmol/L预处理,体外观察EPCs的迁移、黏附功能;建立裸小鼠颈动脉损伤模型,分别移植未处理与100nmol/L的拉西地平预处理的高血压病人外周血EPCs,在体观察EPCs的修复效能。用Realtime RT-PCR及Western-blot检测EPCs表面基因和蛋白的表达情况,探讨拉西地平影响内皮化的分子机制。结果不同浓度的拉西地平预处理高血压病人外周血EPCs,体外迁移和黏附功能较未处理组明显增强,100nmol/L最为显著(p<0.05);100nmol/L的拉西地平预处理的EPCs在体再内皮能力较对照组显著增加(p<0.01)。基因及蛋白水平检测显示,不同浓度的拉西地平处理后,EPCs表面的CXCR4表达增加,100nmol/L最为显著(p<0.001)。结论拉西地平明显改善高血压病人EPCs血管损伤修复能力,可能与CXCR4有关。

Objective To explore the effect of Lacidipine treatment on the endothelial repaircapacity of endothelial progenitor cells（EPCs） from hypertensive patients.Methods Totally 10 patients with essential hypertension and 10 sex and age-matched healthy volunteers were enrolled.Peripheral blood mononuclear cells were isolated and induced to differentiate into EPCs.Migration and adhesion functions of EPCs with or without in vitro lacidipine treatment（10,100 and 1000 nmol/L） were evaluated.In vivo reendothelialization capacity of EPCs from hypertensive patients with or without in vitro lacidipine treatment（100 nmol/L） was examined in a nude mouse model of carotid artery injury.The expression of gene and protein on surface of EPCs were analyzed by Realtime RT-PCR or Western-blot.Results Lacidipine increased in vitro migration and adhesion function of EPCs and 100 nmol/L treated group was the most significant（ P〈0.05）.Transplantation of EPCs pretreated with lacidipine（100 nmol/L） significantly accelerated in vivo reendothelialization（ P〈0.01）.Different concentrations of lacidipine treatment for 12 hours resulted in an upregulation of CXCR4 level in EPCs,especially 100 nmol/L（P〈0.001）.Conclusion Lacidipine treatment can effectively improve endothelial repair capacity of EPCs from patients with essential hypertension.