阈下电刺激促大鼠缺血心肌毛细血管新生的研究

目的：探讨不同频率的阈下电刺激促缺血心肌毛细血管新生的作用及其发生机制。方法：给心肌梗死大鼠发放不同频率的阈下电刺激，观察缺血心肌中毛细血管新生情况，以及血管内皮生长因子(VEGF)的表达、一氧化氮合酶(NOS)活性的变化。结果：(1)25Hz频率的阈下电刺激组，大鼠缺血心肌中毛细血管密度、VHGF mRNA及蛋白质表达、NOS活性均比其它电刺激组及对照组增加。(2)25Hz频率阈下电刺激基础上加用VEGF中和抗体干预后，大鼠缺血心肌毛细血管密度明显减少，NOS活性降低。(3)25Hz频率阈下电刺激基础上加用NOS抑制剂L-NAME干预后，大鼠缺血心肌中VEGF mRNA及蛋白质表达没有改变，但毛细血管密度显著减少。结论：25Hz频率的阈下电刺激可以促进缺血心肌中VEGF表达的上调，导致毛细血管新生；NO可能介导VEGF促血管内皮细胞增殖作用。

The study of angiogenesis induced by electrical stimulation below contraction threshold, in ischemic myocardium

Objective:To study the ischemic myocardial angiogenesis induced by electrical stimulation below contraction threshold.Methods:24 infarcted rats were given electrical stimulation below contraction threshold for 5 days with 10Hz,15Hz,25Hz,50Hz stimulus frequencies.12 other infarcted rats were electrically stimulated with effective stimulus frequency which induced myoardial angiogenesis and treated with VEGF neutralizing antiboby,L-NAME for 5 days.Capillary density(CD),activity of NOS,expression of VEGF mRNA and protein,were detected.Results:CD,activity of NOS,expression of VEGFmRNA and protein in ischemic myocardium were significantly augmented in the 25Hz group compared with the other groups.CD and activity of NOS in ischemic myocardium significantly decreased in 25Hz+VEGF neutralizing antibody group compared with that of the 25Hz group.CD in ischemic myocardium significantly decreased in the 25Hz+L-NAME group compared with that of the 25Hz group,but expression of VEGF mRNA and protein were in the absence of changes the 2 groups.Conclusion:Myocardial angiogenesis induced by electrical stimulation below contraction threshold at 25Hz frequeney is dependent on the expression of VEGF.Nitric oxide can mediate mitogenic effect of VEGF on capillary endothelial cells.