VEGF_(165)基因治疗对心肌梗死大鼠心功能和心肌细胞凋亡的影响

EFFECTS OF VEGF_(165) cDNA INTRAMYOCARDIAL INJECTION ON CARDIAC FUNCTION AND MYOCYTE APOPTOSIS IN MYOCARDIAL INFARCTION OF RATS

目的:探讨直接心肌注射血管内皮生长因子165基因(VEGF165cDNA)对急性心肌梗死大鼠心功能、心肌细胞凋亡及凋亡相关蛋白p53、Fas、Bax和Bcl-2表达的影响。方法:40只雄性SD大鼠结扎左冠状动脉后随机接受VEGF165cDNA(治疗组)或pcDNA3.1(对照组)治疗。于注射2周后测定血流动力学参数、梗死面积、微血管数量、心肌细胞凋亡指数、心肌组织p53、Fas、Bax和Bcl-2蛋白表达的变化。结果:在实验中对照组5只、治疗组8只大鼠死亡,27只进入研究。注射后2周治疗组的平均动脉压、左室收缩压、左室最大收缩或舒张速率和微血管计数显著高于对照组(P<0.05～0.001),而左室舒张末压和梗死面积则显著低于对照组(分别P<0.01和0.05)。治疗组心肌细胞凋亡数量明显少于对照组[(7.6±2.5)%比(14.2±3.4)%,P<0.001],VEGF165cDNA治疗抑制p53、Fas和Bax的表达,促进Bcl-2的表达。结论:直接心肌注射VEGF165cDNA能够明显改善急性心肌梗死大鼠的血流动力学,缩小梗死面积,促进心肌内新血管的形成,减少心肌细胞凋亡,抑制p53、Fas和Bax的表达,促进Bcl-2的表达。TEAPOPTO xing,WuHai,rsity。

Objective:To determine the effects of intramyocardial injection of plasmid VEGF_(165) cDNA on cardiac function, myocyte apoptosis, and expression of p53, Fas, Bax and Bcl-2 in a rat model of acute myocardial infarction.Methods:Forty male Sprague-Dawley rats were subject to left coronary artery ligation and were randomized to receive VEGF_(165) cDNA (treated group, n=20) or pcDNA3.1 (control group, n=20). Hemodynamic parameters, infarct size, intramyocardial microvessels, apoptotic index, p53, Fas, Bax and Bcl-2 expression in myocardium were measured in 2 weeks after injection.Result:Five rats in control, eight in treated group died during the experiment. The remaining 27 rats were included in the study. The mean arterial pressure, left ventricular systolic pressure, maximum rate of left ventricular pressure rise or fall, and microvessel counts in treated group 2 weeks after injection were significantly higher than those in control group (P<0.05 to 0.001), whereas the left ventricular end-diastolic pressure and infarct size in treated group were significantly lower than those in control group (P<0.01 and 0.05, respectively). The number of apoptotic myocytes in treated group was less than that in control group[(7.6±2.5)% vs.(14.2±3.4)%, P<0.001]. VEGF_(165) cDNA treatment signifcantly inhibited p53, Fas and Bax, and increased Bcl-2 expression in myocardium.Conclusion:The current investigation shows that intramyocardial injection of VEGF_(165) cDNA is capable of significantly improving hemodynamics; reducing infarct size, myocyte apoptosis, p53, Fas and Bax expression; promoting myocardial neovascularization and increasing Bcl-2 expression in a rat model of acute myocardial infarction.