The red wine antioxidant resveratrol prevents cardiomyocyte injury following ischemia-reperfusion via multiple sites and mechanisms
The red wine antioxidant resveratrol prevents cardiomyocyte injury following ischemia-reperfusion via multiple sites and mechanisms
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DOI：
10.1089/ars.2007.9.101
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发表时间：
2007-01-01
影响因子：
6.6
通讯作者：
Ritchie, Rebecca H.
中科院分区：
文献类型：
--
作者：
Goh, Siew Simg C.;Woodman, Owen L.;Ritchie, Rebecca H.
目的是全面研究白藜芦醇在缺血再灌注（I-R）损伤期间和之后的心脏保护作用的机制和部位，并确定直接保存心肌细胞是否是心脏保护的重要部位。我们现在提供了第一个明确的证据，证明白藜芦醇通过抑制超氧化物水平和激活钾通道的结合，特异性保护心肌细胞免受 I-R 损伤。无论白藜芦醇在整个损伤期间存在还是仅在恢复时存在，这种保护作用都是显而易见的。此外，白藜芦醇可改善左心室收缩功能的缺血后恢复，减轻心肌损伤，并增加完整心脏中存活激酶 Akt 的心肌活化。此外，白藜芦醇对脉管系统产生直接的浓度依赖性保护作用（血管舒张、超氧化物抑制）并增强内皮依赖性血管舒张。因此，白藜芦醇针对心肌 I-R 的许多后果，包括活性氧的释放、收缩功能恢复的丧失以及内皮依赖性血管舒张受损。先前的证据表明，白藜芦醇可在心脏中引起有效的预处理。鉴于人类的心肌缺血事件通常是不可预测的，因此在损伤期间和/或之后施用白藜芦醇的保护作用也很明显，这一发现为白藜芦醇的临床潜力增加了新的维度。
The objective was a comprehensive investigation of the mechanisms and sites of resveratrol cardioprotection during and following ischemia-reperfusion (I-R) injury, and to determine whether direct preservation of cardiomyocytes is an important site of cardioprotection. We now provide the first definitive evidence that resveratrol specifically protects cardiomyocytes from I-R injury via a combination of suppression of superoxide levels and activation of potassium channels. This protection is apparent whether resveratrol is present for the full duration of the insult or only on recovery. In addition, resveratrol improved postischemic recovery of left ventricular contractile function, attenuated myocardial injury, and increased myocardial activation of the survival kinase Akt in the intact heart. Furthermore, resveratrol elicited direct concentration-dependent protective actions on the vasculature (vasorelaxation, superoxide suppression) and enhanced endothelium-dependent vasodilatation. Resveratrol thus targets a number of consequences of myocardial I-R, including release of reactive oxygen species, loss of recovery of contractile function, and impaired endothelium-dependent vasodilatation. Previous evidence indicates that resveratrol elicits potent preconditioning in the heart. Given that myocardial ischemic events are often unpredictable in humans, the findings that resveratrol protection is also evident when administered during and/or after the insult adds new dimensions to the clinical potential of resveratrol.