hVEGF165腺相关病毒对心肌梗死大鼠心功能的影响

摘要

Objective To determine the effects of intramyocardial injection of rAAV-hVEGF165 on cardiac function in rats with acute myocardial infarction. Methods Eighty-one male Sprague-Dawley rats weighing received a ligation of the left anterior descending artery to induce myocardial infarction(MI) under intraperitoneal anaesthesia. Right after the model preparation, 100μl rAAV-hVEGF165 or saline was intramyocardially injected into three separate sites at the border zone of infarction. The models were divided randomly into four groups;sham operation group ( n = 15) ; saline group (n = 25) ; MI group ( n = 25) ; and VEGF group ( n =16). Echocardiographic data, infarct size, densities of intramyocardial microvessels and VEGF were measured at four weeks after the procedure. Results Three rats in sham operation group,13 rats in MI group,15 rats in saline group,and 7 rats in VEGF group died during the experiment. The remaining 43 rats were analyzed in the study. Infarct sizes in VEGF group were significantly lower than those in MI group and NS group (38. 6±3,0)% vs (42. 5±3. 8)% ,(42. 5±2. 6)%C P <0. 05). Ejection fraction (EF) in VEGF group was significantly higher than that in MI group and NS group (61.11±8. 37}% vs (44.17± 5. 31) % ,(39. 40±5. 48%( P <0. 01). The densities of microvessels were significantly higher in VEGF group than MI group and NS group (522. 38±82. 14) mm2 vs (419. 99±32. 17) mm2 ,(420. 86±16. 50) mm2( P <0. 01). Conclusion The investigation shows that intramyocardial injection of rAAV-hVEGF165 significantly improves cardiac function, reduces infarct size,promotes myocardial neovascularization in rats with acute myocardial infarction.%目的 探讨直接心肌注射基因重组hVEGF165腺相关病毒(rAAV-hVEGF165)对急性心肌梗死大鼠心功能的影响.方法 取81只雄性Sprague-Dawley大鼠,制备急性心肌梗死大鼠模型.将心肌梗死大鼠模型随机分成4组:假手术组15只；心肌梗死组25只;生理盐水组25只；VEGF组16只.生理盐水组和VEGF组分别接受生理盐水或rAAV- hVEGF165 100μl分3点注射于梗死史界处心肌内.于注射4周后测定心肌组织VEGF含量、超声心动图参数、梗死范围、微血管数量、心钠素(atrial natriuretic peptide,ANP)水平.结果 假手术组中3只大鼠、心肌梗死组中13只大鼠、生理盐水组中15只大鼠、VEGF组中7只大鼠死亡,43只大鼠进入研究.VEGF组心肌梗死范围较心肌梗死组和生理盐水组明显减小(38.6±3.0)％ vs (42.5±3.8)％、(42.5±2.6)％(P＜0.05).VEGF组的左心室射血分数显著高于心肌梗死组和生理盐水组(61.11±8.37)％vs (44.17±5.31)％、(39.40±5.48)(P＜0.01).VEGF组心肌组织中VEGF含量较心肌梗死组和生理盐水组有所增加,血管计数显示,VEGF组有更多的新生血管形成(522.38±82.14) mm2 vs (419.99±32.17) mm2、(420.86±16.50) mm2(P＜0.01).结论 梗死区交界处心肌内直接注射rAAV-hVEGF165能够显著改善急性心肌梗死大鼠的心功能,缩小梗死范围,促进心肌内新生血管的形成.