超声微泡联合Ad-EGFP/HIF-1α介导EPCs移植治疗大鼠心肌梗死

Combination of ultrasound microbubbles and Ad-EGFP/HIF-1α mediate EPCs implantation for rat myocardial infarction

目的探讨超声微泡联合Ad-EGFP/HIF-1α介导内皮祖细胞(EPCs)移植治疗大鼠心肌梗死的可行性。方法将Ad-EGFP/HIF-1α转染EPCs。将30只SD大鼠建立心肌梗死模型后随机分为5组:空白对照组(C组)、超声+微泡组(US+MB组)、单纯EPCs组、超声+EPCs组(US+EPCs组)及超声+微泡+EPCs组(US+MB+EPCs组)。EPCs移植后4周,用超声心动图检测大鼠左心室收缩功能,免疫组织化学(I HC)染色法检测CD34的表达及微血管密度(MVD),Western blot检测VEGF蛋白的表达。结果 US+MB+EPCs组射血分数、短轴缩短率高于其他各组(P<0.05),MVD计数高于其他各组(P<0.05)且VEGF蛋白表达水平最高(P<0.05)。结论超声微泡联合Ad-EGFP/HIF-1α介导EPCs移植可通过促进VEGF的高效表达、刺激心肌梗死周边区血管生成等途径改善心肌梗死大鼠的心功能。

Objective To explore the feasibility of mediated endothelial progenitor cells（EPCs） in treating rat acute myocardial infarction by ultrasound microbubbles and Ad-EGFP/HIF-1α.Methods EPCs were transfected by Ad-EGFP/HIF-1α in vitro.Thirty Sprague-Dawley rat models of myocardial infarction were prepared and randomly divided into 5 groups,including blank control（C） group,ultrasound＋microbubbles（US＋MB） group,EPCs group,ultrasound＋EPCs（US＋EPCs） group and ultrasound＋microbubbles＋EPCs（US＋MB＋EPCs） group.All the rats were sacrificed 4 weeks after EPCs implantation.The systolic function of left ventricular was detected by echocardiogram.The CD34 expression was detected by immunohistochemistry（IHC） and the microvessel density（MVD） was determined.The expression of VEGF was respectively detected by Western blot.Results Echocardiography showed ejection fraction and fractional shortening were higher in US＋MB＋EPCs group than those in other groups（P0.05）.The MVD of US＋MB＋EPCs group was the highest among all the groups（P0.05） and the expression of VEGF in US＋MB＋EPCs group was higher than those of other groups（P0.05）.Conclusion Combination of ultrasound microbubbles and recombinant adenovirus Ad-EGFP/HIF-1α can mediate EPCs effectively to the ischemic myocardium,and improve the cardiac function by promoting the expression of VEGF and angiogenesis in rats.