目的:研究内皮祖细胞(EPCs)对生理性缺血训练(PIT)促进远隔缺血心肌侧支循环生成的影响.方法:选择健康新西兰白兔雌雄不拘,体重(2.5±0.5)kg.冠状动脉左室支(LVB)安装特制水囊球,通过充放水制作可控性心肌缺血动物模型.休息1周后将实验动物随机分为6组:假手术组(SO)、单纯肢体缺血组(LIT)、单纯心肌缺血组(MI)、生理性缺血训练组(PIT)、EPCs促进剂组(Pro-EPCs)、EPCs抑制剂组(Inhi-EPCs).SO组不做任何干预,LIT组进行双下肢缺血训练,MI组进行心肌缺血训练,PIT组生理性缺血训练,即心肌缺血同时进行双下肢缺血训练,Pro-EPCs组在PIT组基础上口服EPCs促进剂,Inhi-EPCs组在PIT组基础上口服EPCs抑制剂.训练4周后,取左室支支配区域心肌,采用微球法测定训练前、后缺血区心肌相对侧支循环血流量(RCBF);免疫组化法检测实验终点缺血区毛细血管密度(CD).结果:与实验前相比,MI组、PIT组RCBF值分别增加5.11、19.39(P< 0.05).实验结束时,MI组、PIT组RCBF显著高于SO组和LIT组(P<0.05),PIT组高于MI组(P<0.05),SO组与LIT组无显著性差异(P>0.05).与PIT组比较,Pro-EPCs组RCBF明显增高(P<0.05),Inhi-EPCs组RCBF显著降低(P<0.05).CD结果与RCBF值类似.结论:①生理性缺血训练可促进远隔缺血心肌侧支循环生成.②生理性缺血训练同时,正负向调节内皮祖细胞,可相应促进或抑制远隔缺血心肌侧支循环生成.EPCs是生理性缺血训练促进远隔缺血心肌侧支循环形成过程中的重要细胞机制.
Objective:To investigate the effect of endothelial progenitor cells (EPCs) on collateral circulation formation promoted by physiological ischemic training in remote ischemic myocardium.Method:Healthy male or female New Zealand white rabbits weighing (2.5±0.5)kg were selected.Controllable myocardial ischemia was modelled by a water balloon constrictor implanted on the left ventricular branch(LVB)in a rabbit.One week later,the rabbits were randomly divided into six groups:sham operation group(SO),pure limb ischemia group(LIT),pure myocardial ischemia group(MI),physiological ischemic training group (PIT),PIT with EPCs promoter group(Pro-EPCs),PIT with EPCs inhibitor group(Inhi-EPCs).After four weeks of training,the left ventricular myocardium branch dominated region were taken,relative collateral blood flow (RCBF) measured by microspheres and capillary density(CD) by immunohistochemical assay.Result:Compared with the pre,the RCBF of MI group and PIT group increased 5.11 and 19.39 respectively (P 〈 0.05).At the endpoint,the RCBF of MI group and PIT group was significantly higher than that of SO group and LIT group (P〈 0.05).PIT group had a higher result than the MI group (P 〈 0.05).And the effect was accelerated by EPCs promoter (P〈0.05) and inhibited by EPCs inhibitor (P〈0.05).Capillary density (CD) had a similar result with the RCBF.Conclusion:①Physiological ischemic training can promote the formation of collateral circulation in remote myocardium.②EPCs play a crucial role in this process.