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白葡萄酒诱导的针对缺血再灌注损伤的心脏保护作用是由延长寿命的Akt/FOXO3a/NFκB生存途径介导的。

White wine induced cardioprotection against ischemia-reperfusion injury is mediated by life extending Akt/FOXO3a/NFkappaB survival pathway.

作者信息

Thirunavukkarasu Mahesh, Penumathsa Suresh Varma, Samuel Samson Mathews, Akita Yuzo, Zhan Lijun, Bertelli Alberto A E, Maulik Gautam, Maulik Nilanjana

机构信息

Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, Farmington, CT, USA.

出版信息

J Agric Food Chem. 2008 Aug 13;56(15):6733-9. doi: 10.1021/jf801473v. Epub 2008 Jul 19.

DOI:10.1021/jf801473v
PMID:18642840
Abstract

Recent studies on the protection afforded by moderate wine consumption against cardiovascular diseases have focused mainly on the activity of red wine in view of its high content of antioxidants, especially polyphenols. White wine lacks polyphenols, but it contains other compounds such as hydroxycinnamic acids (caffeic acid) and monophenols (tyrosol), which are known to have antioxidant properties. Therefore, this study was designed to examine the effect of white wine in myocardial ischemic-reperfusion injury. The experimental rats were gavaged with white wine (Soave Suavia "Le Rive" 2004) at a dosage of 6.5 mL/(kg.rat.day) for 30 days. Rats were divided into four groups: control sham (CS), wine-treated sham (WS), control ischemia (I)/reperfusion (R) (CIR), and wine + IR (WIR). All the rats in both IR groups underwent 30 min occlusion of the left anterior descending coronary artery followed by 8, 24 h, and 30 days of reperfusion (R). Significant reduction in infarct size (21 vs 39%, n = 6), cardiomyocyte (274 vs 384 counts/100 HPF, n = 6), and endothelial cell apoptosis (387 vs 587 counts/100 HPF) was observed in WIR as compared with CIR after 24 h of reperfusion. Echocardiography demonstrated significant increased fractional shortening (32 vs 22%) and ejection fraction (60 vs 44%) following 30 days of reperfusion in WIR rats compared to CIR ( n = 6). In addition, increased phosphorylation of AKT, Foxo3a, and eNOS were found in WS and WIR, as compared to their respective controls. The gel-shift analysis demonstrated significant upregulation of DNA binding activity of NF-kappaB in the white wine-treated groups. This report demonstrated for the first time that the white wine mediated cardioprotection in ischemic reperfused myocardium is through the PI-3kinase/Akt/FOXO3a/e-NOS/NF-kappaB survival pathway.

摘要

近期关于适量饮用葡萄酒对心血管疾病的保护作用的研究主要集中在红酒的活性上,因为红酒富含抗氧化剂,尤其是多酚类物质。白葡萄酒缺乏多酚类物质,但它含有其他化合物,如羟基肉桂酸(咖啡酸)和单酚类物质(酪醇),已知这些物质具有抗氧化特性。因此,本研究旨在探讨白葡萄酒对心肌缺血再灌注损伤的影响。实验大鼠以6.5 mL/(kg·大鼠·天)的剂量灌胃白葡萄酒(索阿维苏阿维亚“勒里夫”2004年份),持续30天。大鼠分为四组:对照假手术组(CS)、葡萄酒处理假手术组(WS)、对照缺血/再灌注组(CIR)和葡萄酒+缺血再灌注组(WIR)。两个缺血再灌注组的所有大鼠均接受左冠状动脉前降支30分钟的阻断,随后进行8小时、24小时和30天的再灌注(R)。再灌注24小时后,与CIR组相比,WIR组的梗死面积(21%对39%,n = 6)、心肌细胞(274个对384个计数/100高倍视野,n = 6)和内皮细胞凋亡(387个对587个计数/100高倍视野)显著减少。超声心动图显示,与CIR组相比(n = 6),WIR组大鼠再灌注30天后的缩短分数(32%对22%)和射血分数(60%对44%)显著增加。此外,与各自的对照组相比,WS组和WIR组中AKT、Foxo3a和eNOS的磷酸化增加。凝胶迁移分析表明,白葡萄酒处理组中NF-κB的DNA结合活性显著上调。本报告首次证明,白葡萄酒介导的缺血再灌注心肌的心脏保护作用是通过PI-3激酶/Akt/FOXO3a/e-NOS/NF-κB存活途径实现的。

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