环氧化酶Ⅱ、神经型一氧化氮合酶介导了心肌缺血预处理延迟性保护作用终末阶段

COX-2 or nNOS Mediates Cardioprotection During the Final Stage of the Late Phase of Ischemic Preconditioning

本研究采用在体家兔冠状动脉阻断的缺血／复灌损伤模型，研究心肌缺血预处理（IP）延迟性保护作用终末阶段（IP后48-72h），以及神经型一氧化氮合酶（nNOS）、诱生型一氧化氮合酶（iNOS）、环氧化酶1I（Cyelcoxy-genase-2，COX-2）是否中介了此过程。研究发现与单纯缺血／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）、6-酮-PGE1a（6-Keto-PGF1a）含量，促进左室收缩压（LVSP）、左室压最大上升速率（＋dP／dtmax）和左室压最大下降速率（-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）、环氧化酶Ⅱ特异性抑制剂塞来昔布（celecoxib，CEL）阻断了IP后72h的心肌保护作用。结果表明：IP后72h心肌保护作用依然存在，COX-2、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 studies was to investigate the cardioprotection of late IP at 72 h and determine the involvement of iNOS, nNOS and COX-2 in this protection. Conscious rabbits were preconditioned with three cycles of 5- minute coronary occluslon/5-minute reperfusion. The myocardial infarct area in the rabbits preconditioned 72 h earlier was significantly smaller than that in control rabbits. The activity of lactate dehydrogenase （LDH） and the level of 6-Keto- PGF1α in the rabbits preconditioned 72 h earlier were lower than those in control rabbits. The left ventricular systolic pressure （LVSP） and maximal velocity of contraction and relaxation （ ＋ dP/dtmax） were improved in rabbits preconditioned 72 h earlier. The nNOS-selective inhibitors N-pmpyl-L-arginine and selective cyclooxygenase-2 （ODX-2） inhibitor cetecoxib completely blocked the protection of late IP at 72 h, whereas the iNOS selective inhibitor S-methylisothiourea had no effect. In conclusion, the cardioprotection observed in the final stage of late IP （72 hours） is mediated by nNOS or COX-2, but not by iNOS.