The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats.
The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats.
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在清醒大鼠中，通过 COX-2 介导的机制进行后处理可增强缺血预适应后期的心脏保护作用。
DOI：
10.1152/ajpheart.00858.2007
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Tang,Xian-Liang
中科院分区：
文献类型：
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作者：
Sato,Hiroshi;Bolli,Roberto;Rokosh,GreggD;Bi,Qiuli;Dai,Shujing;Shirk,Gregg;Tang,Xian-Liang
本研究旨在确定晚期预处理（PC）与后处理相结合是否能增强梗死面积的减少。将慢性仪器大鼠分配到45分钟（子集1）或60分钟（子集2）冠状动脉闭塞，然后再灌注24小时。在每个亚组中，大鼠未接受进一步干预（对照）或在闭塞前24 h进行预处理（PC），在闭塞后再灌注开始时进行后处理，或在后处理前10 min进行预处理和后处理（PC +后处理），不使用（PC +后处理）或使用考克斯-2抑制剂塞来昔布（3 mg/kg ip; PC +后处理+塞来昔布）。在另外5组（对照组、PC组、后处理组、PC +后处理组和PC +后处理+塞来昔布组）再灌注45分钟后，测量心肌环氧化酶-2（考克斯-2）蛋白表达和考克斯-2活性（以心肌PGE 2水平评估）。单独PC在45分钟闭塞后减少梗死面积，但在60分钟闭塞后不减少。单独的后处理在两种情况下都不能减少梗死面积。然而，在这两种情况下，晚期PC和后处理的组合导致了强大的梗死保留效应，这表明了额外的心脏保护作用。塞来昔布完全消除了两种情况下联合干预的梗死保留效应。晚期胰腺癌组织中考克斯-2蛋白表达和PGE 2含量增加。PGE 2含量（但不是考克斯-2蛋白）进一步增加的联合干预，表明后处理增加了考克斯-2的活性诱导的晚期PC。总之，晚期PC和后处理的组合产生了额外的保护作用，可能是由于后处理诱导的考克斯-2活性增强。
The present study sought to determine whether the combination of late preconditioning (PC) with postconditioning enhances the reduction in infarct size. Chronically instrumented rats were assigned to a 45-min (subset 1) or 60-min (subset 2) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control) or were preconditioned 24 h before occlusion (PC), postconditioned at the onset of reperfusion following occlusion, or preconditioned and postconditioned without (PC + postconditioning) or with the COX-2 inhibitor celecoxib (3 mg/kg ip; PC + postconditioning + celecoxib) 10 min before postconditioning. Myocardial cyclooxygenase-2 (COX-2) protein expression and COX-2 activity (assessed as myocardial levels of PGE2) were measured 6 min after reperfusion in an additional five groups (control, PC, postconditioning, PC + postconditioning, and PC + postconditioning + celecoxib) subjected to a 45-min occlusion. PC alone reduced infarct size after a 45-min occlusion but not after a 60-min occlusion. Postconditioning alone did not reduce infarct size in either setting. However, the combination of late PC and postconditioning resulted in a robust infarct-sparing effect in both settings, suggesting additive cardioprotection. Celecoxib completely abrogated the infarct-sparing effect of the combined interventions in both settings. Late PC increased COX-2 protein expression and PGE2content. PGE2content (but not COX-2 protein) was further increased by the combination of both interventions, suggesting that postconditioning increases the activity of COX-2 induced by late PC. In conclusion, the combination of late PC and postconditioning produces additive protection, likely due to a postconditioning-induced enhancement of COX-2 activity.