一氧化氮对心肌缺血/再灌注损伤细胞凋亡和心功能的影响

THE EFFECTS OF NITRIC OXIDE ON CARDIAC APOPTOSIS AND FUNCTION DURING MYOCARDIAL/REPERFUSION INJURY

目的 :采取促进或抑制NO的方法 ,了解在重复可逆性心肌缺血 /再灌注所致的心肌顿抑时 ,血液中一氧化氮(NO)的动态变化与细胞顿抑及心功能的影响。方法 :新西兰兔 15只 ,随机分为 3组 (n =5 ) :对照组、在静脉内注射NO合成底物L 精氨酸为L Arg组、静脉注射一氧化氮合酶抑制剂L 硝基 精氨酸为L NNA组。用戊巴比妥钠静脉注射麻醉后 ,结扎前降支制成心肌缺血 /再灌注模型 ,用电子自旋共振法测定血液中NO含量 ,同时记录左心室最大上升速率dp/dtmax。将兔心肌缺血 10min ,共 3次 ,第 1、2次缺血后再灌注 10min ,第 3次缺血后再灌注 12 0min。结果 :第 1次缺血 /再灌注 5min时NO升高的顺序依次为L Arg组最大、对照组次之 ,而L NNA组较缺血前降低。而dp/dtmax明显下降的是L Arg组最大、对照组次之、L NNA组最小。细胞凋亡指数 :L Arg组最大 ,对照组次之、L NNA组最小。结论 :再灌注早期NO的大量生成及细胞凋亡参与加重心肌顿抑的过程。

Aim: The observation of the relationship between the level of NO detected by ESR in the blood and the myocardial apoptosis and function caused by the recurrent,reversible myocardial ischemia/reperfusion injury. Methods: Fifteen New Zealand white rabbits were randomly divi- ded into three groups(n=5): ①control group,②L-Arg group,③L-NNA group. The rabbits were anesthetized with intravenous pentobarbital. A suture ligature was passed around the left anterior descending coronary artery(LAD),so it could be snare occluded and reperfused. The LAD was occluded for 10 min three times,the first and second occlusions were followed by 10 min of reflow,after the third occlusion,the reperfusion was 120 min. Results: In all groups dp/dt max began to decrease at 5 min after the first ischemia. But compared with control group at 5 min after first reperfusion: in L-Arg group NO and apoptosis level were elevated but dp/dt max decreased significantly. In L-NNA group NO and apoptosis decreased significantly,dp/dt max improved significantly. Conclusion: The fact that the level of NO and apoptosis elevated suggested that they had taken part in the process of myocardial stunning.