培哚普利对急性心肌梗死伴2型糖尿病患者内皮祖细胞动员及预后的影响

目的观察应用培哚普利治疗急性心肌梗死(AMI)伴2型糖尿病(T2DM)患者的预后,血浆血管内皮生长因子(VEGF)、基质细胞衍生因子(SDF-1α)水平,骨髓内皮祖细胞(EPC)动员情况。方法将20例AMI伴T2DM患者随机分为培哚普利组(10例,予口服培哚普利4mg/d)及对照组(10例,未予培哚普利)。采用密度梯度离心法分离外周血单个核细胞,应用流式细胞仪检测AMI不同时间点急诊经皮冠状动脉介入治疗(PCI)前,PCI后1、3、5、7、14和28d]外周静脉血中CD45-/low+/CD34+/CD133+/KDR+早期EPC数量。采用酶联免疫吸附法检测血浆中VEGF、SDF-1α及超敏C反应蛋白(hs-CRP)水平。结果培哚普利组在PCI后7d的外周静脉血中EPC数量为(211±78)个/1×106,显著高于对照组的(147±57)个/1×106(P<0.05),且在PCI后5d较PCI前显著升高(P<0.05)。培哚普利组在PCI后5、7d的血浆中VEGF水平(172±72)、(183±63)ng/L]均显著高于同时间点的对照组分别为(105±63)、(77±37)ng/L,P值均<0.05]。培哚普利组在PCI后7d(高峰点)的SDF-1α水平为(3296±680)ng/L,显著高于同时间点的对照组(2115±570)ng/L,P<0.05]。培哚普利组在PCI后3d(高峰点)的hs-CRP水平为(26.2±6.5)mg/L,显著低于同时间点的对照组(33.8±10.6)mg/L,P<0.05]。随访6个月时培哚普利组的左心室射血分数(LVEF)为0.491±0.059,显著高于入院时的0.469±0.051(P<0.05);对照组LVEF分别为0.482±0.054、0.479±0.052,差异无统计学意义(P>0.05)。结论使用培哚普利治疗AMI伴T2DM患者,可改善其组织缺血后SDF-1α、VEGF-EPC动员通路障碍,并改善其预后。

Effect of perindopril on mobilization of endothelial progenitor cells and prognosis in patients with acute myocardial infarction and type 2 diabetes

Objective To observe the levels of plasma vascular endothelial growth factor(VEGF),stromal cell-derived factor-1α(SDF-1α),the mobilization of endothelial progenitor cell(EPC) and prognosis in patients with acute myocardial infarction(AMI) and type 2 diabetics after treatment with peridopril.Methods Twenty AMI patients with type 2 diabetes mellitus,who underwent percutaneous coronary invention(PCI),were randomly divided into peridopril group(n=10,peridopril 4 mg/d) and control group(n=10,no peridopril).Peripheral blood mononuclear cells(PBMCs) were isolated with density gradient centrifugation.Circulating CD45-/low+/CD34+/CD133+/KDR+ early EPC count in PBMCs were quantified by flow cytometry before PCI and on day 1,3,5,7,14,28 after PCI.Plasma levels of VEGF,SDF-1α and high sensitivity C-reactive protein(hs-CRP) were measured by enzyme linked immunosorbent assay(ELISA).Results The circulating EPC count in perindopril group was significantly more than that in control group at day 7 after PCI(211±78] /1×106 vs.147±57] /1×106,P <0.05).Compared with that before PCI,EPC was significantly increased at day 5 after PCI in both groups(P<0.05).Plasma VEGF level in perindopril group was significantly higher than that in control group at day 5(172±72] ng/L vs.105±63] ng/L,P<0.05) and day 7(183±63] ng/L vs.77±37] ng/L,P<0.05) after PCI,so was the SDF-1α at day 7 after PCI(3 296±680] ng/L vs.2 115±570] ng/L,P <0.05).However,hs-CRP in perindopril group was significantly lower than that in control group at day 3 after PCI(26.2±6.5] mg/L vs.33.8±10.6] mg/L,P<0.05).Left ventricular ejection fraction(LVEF) in perindopril group was significantly higher than that on admission six month after AMI(0.491±0.059 vs.0.469±0.051,P<0.05),but there was no significant difference in LVEF at the two time points in control group(0.482±0.054 vs.0.479±0.052,P>0.05).Conclusion Perindopril can improve the abnormal mobilization of SDF-1α and VEGF-EPC after ischemia and the prognosis in AMI patients with type 2 diabetes mellitus.