奥美沙坦酯对急性心肌梗死大鼠内皮祖细胞动员的影响

Effect of olmesartan medoxomil on endothelial progenitor cells mobilization in rats with acute myocardial infarction

目的:探讨奥美沙坦酯对急性心肌梗死(AMI)大鼠骨髓内皮祖细胞(endothelial progenitor cells,EPCs)动员的影响。方法:结扎SD大鼠左冠状动脉前降支制作AMI模型,将术后24 h存活的24只大鼠随机分为3组:AMI组、奥美沙坦酯1 mg·kg-1·d-1组(OML组)和奥美沙坦酯3 mg·kg-1·d-1组(OMH组);另设假手术组(8只)作为对照。灌胃给药共2周。大鼠尾动脉血压计测量大鼠收缩压,ELISA法测定血清血管内皮生长因子(VEGF)含量,以DiI标记的乙酰化低密度脂蛋白(DiI-acLDL)及FITC标记的单叶豆凝集素1(FITC-BS-1)双色荧光标记鉴定循环及骨髓EPCs并对其计数。结果:在术前,术后24 h、1周及2周各组大鼠尾动脉收缩压之间差异无统计学意义;与假手术组比较,AMI组、OML组和OMH组的血清VEGF含量、循环和骨髓EPCs数量均明显升高;与AMI组比较,OML组和OMH组血清VEGF含量无明显变化,循环和骨髓EPCs数量却明显增加。结论:大鼠AMI后2周骨髓EPCs的动员增加,奥美沙坦酯能显著促进AMI大鼠骨髓EPCs的动员,增加循环EPCs数量,此效应与VEGF途径及血压降低无明显相关。

Objective：To investigate the effect of olmesartan medoxomil on endothelial progenitor cells （EPCs） mobilization in rats with acute myocardial infarction （AMI）. Method：Myocardial infarction （MI） was induced by ligation of the left coronary artery in SD rats. After 24 h, surviving rats were randomized to AMI group, olmesartan medoxomil group low dose（1 mg· kg^-1 · d^-1） and olmesartan medoxomil high dose group （3 mg · kg^-1· d^- 1）. Sham-operated rats were induced as control group. Systolic blood pressure were measured in conscious rats with tailcuff method. Two weeks after MI, the number of circulating and bone marrow EPCs was determined by double staining for DiI-acLDL and FITC-BS-1. Serum VEGF levels were determined by ELISA. Result： There was no statistical significance on the difference of systolic blood pressure during the treatment period. Two weeks after MI, compared with the sham group, serum VEGF levels, circulating and bone marrow EPCs were significantly increased in the AMI, the OML and the OMH groups. Compared with the AMI group, there was no difference on serum VEGF level in the olmesartan-treated group, the number of circulating and bone marrow EPCs increased significantly. Conclusion： Serum VEGF and bone marrow EPCs was increased significantly 2 weeks after MI and the number of circulating EPCs was increased concomitantly 2 weeks after MI. Olmesartan medoxomil could amplify mobilization of EPCs and increase the number of circulating EPCs independently on blood pressure lowering and VEGF.