一氧化氮合酶在心肌缺血预处理延迟性保护作用终末阶段中的作用

The Role of nNOS in Cardio-protection in the Final Stage of the Late Phase of Ischemic Preconditioning

目的:研究心肌缺血预处理(IP)延迟性保护作用终末阶段(IP后48h至72h)的机制,以及神经型一氧化氮合酶(nNOS)、诱生型一氧化氮合酶(iNOS)是否中介了此过程。方法:采用在体家兔冠状动脉阻断的缺血/复灌损伤模型,测定心肌梗死面积、冠脉流出液中乳酸脱氢酶(LDH)和肌酸激酶(CK)含量及各项心室力学指标。结果:与单纯缺血/复灌组相比,IP后72h,明显降低心脏缺血/复灌后的梗死面积和血浆中乳酸脱氢酶(LDH)、肌酸激酶(CK)的含量,促进左室收缩压(LVSP)、最大左室收缩速率(+dP/dtmax)和最大左室舒张速率(-dP/dtmax)的恢复。使用iNOS的特异性抑制剂S-methylisothiourea sulfate(SMT)不能阻断IP后72h心肌保护作用。而nNOS的特异性抑制剂N-propyl-L-arginine(NPA)、NOS的非特异性抑制剂NG-硝基-L-精氨酸甲酯(L-NAME)阻断了IP后72h心肌保护作用。结论:IP后72h心肌保护作用依然存在,nNOS介导了心肌缺血预处理延迟性保护作用终末阶段,而与iNOS无关。

The aim of the present study was to investigate the cardio-protection of late PC at 72 hours and determine the involvement of iNOS and nNOS in this protection.Conscious rabbits were preconditioned with three cycles of 5-minute coronary occlusion/5-minute reperfusion.Myocardial infarct size was significantly smaller in rabbits preconditioned 72 hours earlier than in control rabbits.Lactate dehydrogenase（LDH） and activities of creatine kinase（CK） were lower in rabbits preconditioned 72 hours earlier than in control rabbits.Left ventricular systolic pressure（LVSP） and maximal velocity of contraction and relaxation（±dP/dtmax） were improved in rabbits preconditioned 72 hours earlier.The nNOS-selective inhibitors N-propyl-L-arginine completely blocked the protection of late IP at 72 hours,whereas the iNOS selective inhibitor S-methylisothiourea had no effect.In conclusion,the cardio-protection observed in the final stage of late IP（72 hour） is mediated by nNOS not by iNOS.