Pharmacological preconditioning with resveratrol: role of nitric oxide (Retracted Article)
Pharmacological preconditioning with resveratrol: role of nitric oxide (Retracted Article)
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DOI：
10.1152/ajpheart.01012.2001
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发表时间：
2002-06-01
影响因子：
4.8
通讯作者：
Das, DK
中科院分区：
文献类型：
--
作者：
Hattori, R;Otani, H;Das, DK
白藜芦醇（反式-3，4 '，5-三羟基芪）是一种新近发现的葡萄多酚类抗氧化剂，已被发现可保护心脏免受缺血再灌注损伤。本研究试图通过研究白藜芦醇预处理心脏的能力来确定心脏保护的机制。将离体大鼠心脏随机分为6组：I组仅用Kreb-Henseleit缓冲液（KHB）灌流15 min，II组用10 μ M白藜芦醇灌流，III组用10 μ M白藜芦醇加100 μ M一氧化氮（NO）合酶（NOS）抑制剂N-G-硝基-L-精氨酸甲酯（L-NAME）灌流; IV组灌注10 μ M白藜芦醇加100 μ M氨基胍（AG），一种诱导型NOS（iNOS）阻断剂; V和VI组分别由灌注L-NAME和AG的心脏组成。然后将灌注切换到工作模式，并使所有心脏整体缺血30 min，随后再灌注2 h。用白藜芦醇预处理心脏提供了心脏保护作用，如通过改善缺血后心室功能恢复（发展的压力和主动脉流量）和减少心肌梗死面积和心肌细胞凋亡所证明的。白藜芦醇介导的心脏保护作用被L-NAME和AG完全消除。在一项单独的研究中，检查心脏的iNOS mRNA诱导。白藜芦醇诱导iNOS mRNA的表达在再灌注后30 min开始，稳定增加至再灌注60 min，然后逐渐减少至再灌注后2 h。用AG预灌注心脏几乎完全阻断了iNOS的诱导。我们的研究结果表明，白藜芦醇可以通过NO依赖的方式预处理心脏。
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 muM resveratrol; group III was perfused with 10 muM resveratrol plus 100 muM N-G-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide (NO) synthase (NOS) inhibitor; group IV was perfused with 10 muM resveratrol plus 100 muM 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.