一氧化氮及其合酶在心肌缺血再灌注损伤中作用的研究

The effect of nitric oxide and its synthase on myocardial ischemic reperfusion injury

目的：用鼠的离体工作心脏研究心肌缺血再灌注损伤中一氧化氮（ＮＯ） 、ＮＯ 合酶（ＮＯＳ） 的作用。方法：ＲＴＰＣＲ 定量检测心肌组织结构型ＮＯＳ（ｃＮＯＳ） 的ｍＲＮＡ 表达，测定心肌组织的ｃＮＯＳ、诱导型ＮＯＳ（ｉＮＯＳ） 及冠状动脉（ 冠脉） 流出液的ＮＯ，同时检测心脏缺血再灌注前后的心功能变化。并分别于冷停跳液中加用缓激肽（ＢＫ） 、Ｌ精氨酸及ＢＫ 加Ｌ精氨酸，观察其对心肌缺血再灌注损伤的影响。结果：心肌缺血再灌注后，ｃＮＯＳ的ｍＲＮＡ 表达下调，ｃＮＯＳ活性下降，ｉＮＯＳ活性升高，ＮＯ 量减少。ＢＫ 处理组与缺血再灌注的对照组相比，ｃＮＯＳ活性升高，ＮＯ 分泌增多，心功能恢复好转。Ｌ精氨酸处理组与上述对照组相比，ＮＯ 增加，但心功能恢复率反而下降。ＢＫ 加Ｌ精氨酸处理组与ＢＫ 组相比，ＮＯ 及心功能恢复率更高。结论：ｃＮＯＳ的ｍＲＮＡ 表达下调及ＮＯＳ 同功酶变化可能是心肌缺血再灌注损伤的重要机制之一，ＮＯ 对心肌具有“保护”和“毒性”的双重作用，激活ｃＮＯＳ具有心肌保护作用。

Aim:The study was focused on the effect of nitric oxide(NO) and NO synthase (NOS) on the isolated working rat heart after ischemic reperfusion injury.Methods:The gene expression of constitutive NOS (cNOS) was quatified by reverse trancription-polymerase chain reaction (RT-PCR).The myocardial NOS content,the NO in effluent samples from coronary sinus was measured and the cardiofunction was assessed before and after ischemic reperfusion.The effects of Bradykinin(BK),L-argininne and BK+L-arginine on myocardial ischemic reperfusion injury was evaluated.Results:The study demonstrated that the expression of cNOS mRNA was downregulated and NO,cNOS were reduced,but inducible NOS(iNOS) increased during ischemic reperfusion injury.In BK-treated group, compared with the control group of ischemic reperfusion,NO and NOS were increased,the recovery of myocardial function was improved. Compared with the control group,NO was increased in L-arginine-treated group,but the recovery rate of myocardial function was decreased .In BK+L-arginine-treated group,compared with BK-treated group,NO was increased and the recovery of myocardial function was improved significantly.Conclusion:These results indicated that down-regulation of expression of cNOS mRNA and the change of isozymes of NOS could be one of the important mechanisms for the myocardial ischemic reperfusion injury.NO is double- edged but increasing cNOS may have effect of myocardial protection.