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无酒精红葡萄酒通过调节Akt1和蛋白激酶Cα/βII抑制异丙肾上腺素诱导的大鼠心脏重塑。

Alcohol-free red wine inhibits isoproterenol-induced cardiac remodeling in rats by the regulation of Akt1 and protein kinase C alpha/beta II.

作者信息

Palfi Anita, Bartha Eva, Copf Laszlo, Mark Laszlo, Gallyas Ferenc, Veres Balazs, Kalman Endre, Pajor Laszlo, Toth Kalman, Ohmacht Robert, Sumegi Balazs

机构信息

Division of Cardiology, First Department of Medicine, Medical School of Pecs, University of Pecs, Pecs, Hungary.

出版信息

J Nutr Biochem. 2009 Jun;20(6):418-25. doi: 10.1016/j.jnutbio.2008.04.009. Epub 2008 Jul 24.

DOI:10.1016/j.jnutbio.2008.04.009
PMID:18656339
Abstract

There is increasing evidence that moderate consumption of red wine containing high amount of polyphenols and anthocyanins is associated with decreased incidence of cardiovascular morbidity and mortality. Therefore, we hypothesized that cardiac hypertrophy and fibrosis as well as Akt (protein kinase B, PKB) and protein kinase C (PKC) cascades can be beneficially influenced by an alcohol-free red wine (AFRW) extract rich in 14 types of polyphenols and 4 types of anthocyanins during cardiac remodeling. To test this assumption, rats were treated with isoproterenol (ISO) to induce postinfarction remodeling and were given tap water or AFRW ad libitum for 8 weeks. Control rats received vehicle instead of ISO. Heart mass/body mass and ventricle mass/body mass ratios, diameter of cardiomyocytes, phosphorylation of PKC alpha/beta II and protein kinase B/Akt, and deposition of collagen type III were determined from the hearts of all four groups of rats. All measured gravimetric parameters, myocyte diameters and the amount of collagen type III decreased, and the phosphorylation of PKC alpha/beta II was reduced in the ISO+AFRW group compared to the ISO group. AFRW induced activation of Akt, one of the best characterized cytoprotective pathways even without ISO treatment, and this activation was further increased in the ISO+AFRW group. These data suggest that AFRW treatment has a protective effect on hearts undergoing postinfarction remodeling by repressing hypertrophy-associated increased phosphorylation of PKC alpha/beta II and by activating Akt, providing a molecular mechanism for the cardioprotective effect of red wine polyphenols.

摘要

越来越多的证据表明,适度饮用富含大量多酚和花青素的红酒与心血管疾病发病率和死亡率的降低有关。因此,我们推测,在心脏重塑过程中,富含14种多酚和4种花青素的无醇红酒(AFRW)提取物可对心脏肥大、纤维化以及Akt(蛋白激酶B,PKB)和蛋白激酶C(PKC)级联产生有益影响。为了验证这一假设,用异丙肾上腺素(ISO)处理大鼠以诱导梗死后重塑,并随意给予它们自来水或AFRW,持续8周。对照大鼠接受载体而非ISO。测定了所有四组大鼠心脏的心脏质量/体重和心室质量/体重比、心肌细胞直径、PKCα/βII和蛋白激酶B/Akt的磷酸化以及III型胶原蛋白的沉积。与ISO组相比,ISO+AFRW组中所有测量的重量参数、心肌细胞直径和III型胶原蛋白的量均降低,PKCα/βII的磷酸化也减少。即使在没有ISO处理的情况下,AFRW也能诱导Akt(最具特征的细胞保护途径之一)的激活,并且在ISO+AFRW组中这种激活进一步增强。这些数据表明,AFRW处理通过抑制肥大相关的PKCα/βII磷酸化增加和激活Akt,对经历梗死后重塑的心脏具有保护作用,为红酒多酚的心脏保护作用提供了分子机制。

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