Hattori Reiji, Otani Hajime, Maulik Nilanjana, Das Dipak K
Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110, USA.
Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H1988-95. doi: 10.1152/ajpheart.01012.2001.
Resveratrol (trans-3,4',5-trihydroxystilbene), a recently described grape-derived polyphenolic antioxidant, has been found to protect the heart from ischemic-reperfusion injury. The present study sought to determine the mechanism of cardioprotection by investigating the ability of resveratrol to precondition the heart. Isolated perfused rat hearts were randomly divided into six groups: group I was perfused for 15 min with Kreb-Henseleit buffer (KHB) only; group II was perfused with 10 microM resveratrol; group III was perfused with 10 microM resveratrol plus 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide (NO) synthase (NOS) inhibitor; group IV was perfused with 10 microM resveratrol plus 100 microM aminoguanidine (AG), an inducible NOS (iNOS) blocker; and groups V and VI consisted of hearts perfused with L-NAME and AG, respectively. The perfusion was then switched to working mode, and all hearts were made globally ischemic for 30 min followed by 2 h of reperfusion. Preconditioning of the hearts with resveratrol provided cardioprotection as evidenced by improved postischemic ventricular functional recovery (developed pressure and aortic flow) and reduced myocardial infarct size and cardiomyocyte apoptosis. Resveratrol-mediated cardioprotection was completely abolished by both L-NAME and AG. In a separate study, hearts were examined for iNOS mRNA induction. Resveratrol caused an induction of the expression of iNOS mRNA beginning at 30 min after reperfusion, increasing steadily up to 60 min of reperfusion, and then decreasing progressively up to 2 h after reperfusion. Preperfusion of the hearts with AG almost completely blocked the induction of iNOS. The results of our study demonstrate that resveratrol can pharmacologically precondition the heart in a NO-dependent manner.
白藜芦醇（反式 - 3,4',5 - 三羟基芪）是一种最近被描述的源自葡萄的多酚类抗氧化剂，已被发现可保护心脏免受缺血再灌注损伤。本研究旨在通过研究白藜芦醇预处理心脏的能力来确定其心脏保护机制。将离体灌注的大鼠心脏随机分为六组：第一组仅用克雷布斯 - 亨塞尔特缓冲液（KHB）灌注15分钟；第二组用10微摩尔白藜芦醇灌注；第三组用10微摩尔白藜芦醇加100微摩尔N(G)-硝基 - L - 精氨酸甲酯（L - NAME）灌注，L - NAME是一种非选择性一氧化氮（NO）合酶（NOS）抑制剂；第四组用10微摩尔白藜芦醇加100微摩尔氨基胍（AG）灌注，AG是一种诱导型NOS（iNOS）阻滞剂；第五组和第六组分别由用L - NAME和AG灌注的心脏组成。然后将灌注切换到工作模式，所有心脏均进行30分钟的全心缺血，随后再灌注2小时。白藜芦醇对心脏的预处理提供了心脏保护，表现为缺血后心室功能恢复（发展压力和主动脉血流）改善，心肌梗死面积减小，心肌细胞凋亡减少。L - NAME和AG均完全消除了白藜芦醇介导的心脏保护作用。在另一项研究中，检测了心脏中iNOS mRNA的诱导情况。白藜芦醇在再灌注后30分钟开始诱导iNOS mRNA表达，在再灌注60分钟时稳定增加，然后在再灌注2小时内逐渐下降。用AG对心脏进行预灌注几乎完全阻断了iNOS的诱导。我们的研究结果表明，白藜芦醇可通过依赖NO的方式对心脏进行药理学预处理。
