阿司匹林对大鼠缺血心肌血管生成及内皮祖细胞动员的影响

Effect of aspirin on angiogenesis and endothelial progenitor cell mobilization in rat ischemic myocardium

目的观察阿司匹林对大鼠缺血心肌血管生成和内皮祖细胞(endothelial progen itor cells,EPCs)动员的影响和可能机制。方法实验大鼠分为正常对照组、假手术组、心肌缺血加大剂量阿司匹林组、心肌缺血加小剂量阿司匹林组和单纯心肌缺血组。心肌缺血组和假手术组于术后一周从心腔内取血测血管内皮生长因子(VEGF),外周血分离单个核细胞培养计数EPCs,28 d后取缺血区心肌免疫组化法测毛细血管密度。结果单纯心肌缺血组和假手术组与正常对照组相比,血浆VEGF显著增多[(101.51±16.97)、(94.67±11.78)vs(80.07±10.32),(P<0.05)];心肌缺血加小剂量阿司匹林组与正常对照组相比,外周血EPCs显著增多[(42±7)vs(20±6),(P<0.05)];单纯心肌缺血组与正常对照组相比,毛细血管密度显著增加[(600±104)vs(431±73),(P<0.05)];大剂量阿司匹林抑制了因缺血导致的VEGF、EPCs和毛细血管密度的增加分别由缺血时的(101.51±16.97)、(46±9)、(600±104)降至(70.76±10.15)、(23±6)、(431±80),(P<0.05)。结论大剂量阿司匹林可通过抑制VEGF的表达,抑制大鼠缺血心肌的血管生成和因缺血和损伤导致的EPCs的动员。

Objective To study the effect and mechanism of aspirin on angiogenesis and endothelial progenitor cell mobilization in rat ischemic myocardium. Methods SD female rats were randomly divided into 5 groups： control group, sham operation group, only myocardial ischemia group, myocardial ischemia ＋ aspirin of large dose （60 mg · kg^-1 · d ^-1 ） group and myocardial ischemia ＋ aspirin of small dose （5 mg · kg^-1 · d ^-1） group. On postoperative day 7, endothelial progenitor cells （EPCs） and plasma VEGF were measured. On postoperative day 28, capillary densities were also detected in ischemic myocardium and normal myocardium of left ventricle. Results In only myocardial ischemia group and sham operation group, plasma VEGF [ （101.51 ±16.97） and （94.67±11.78） vs （80.07 ±10.32）, P〈0.05] and EPCs [（46±9） and （38±8） vs （20 ± 6）, P 〈 0. 05 ] increased on the baseline of normal controls. In myocardial ischemia ＋ aspirin of small dose group, EPCs increased more than that of control group [ （42 ±7） vs （20±6）, P〈0.05]. In only myocardial ischemia group, capillary densities increased as compared with that of control group [ （600 ± 104） vs （431 ± 73 ）, P 〈 0. 05 ]. The increase of plasma VEGF, EPCs and capillary densities after myocardial ischemia was inhibited by large-dose aspirin but not by small-dose aspirin. Conclusion Aspirin of large dose （60 mg· kg^-1· d^-1 ） can inhibit angiogenesis and endothelial progenitor cell mobilization by attenuating VEGF in rat isehemic myocardium.