Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation.

Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation.
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DOI:
10.1371/journal.pone.0113716
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Hao LP
Hao LP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Peng XL;Qu W;Wang LZ;Huang BQ;Ying CJ;Sun XF;Hao LP

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血管内皮通透性增高是内皮功能障碍的表现之一。白藜芦醇(Resveratrol,Res)被认为是保护内皮功能的有益物质。然而,目前,Res对内皮功能障碍-高通透性的确切保护作用及其机制尚未完全阐明。本研究旨在探讨Res对内皮细胞高通透性的改善作用及其对Caveolin-1(Cav-1)/内皮型一氧化氮合酶(eNOS)通路的影响。成年雄性Wistar大鼠用正常或高脂肪/蔗糖饮食(HFS)加或不加Res处理13周。HFS和体外高糖处理分别增加大鼠主动脉、心脏、肝脏和肾脏以及培养的牛主动脉内皮细胞(BAECs)的通透性增高,而Res处理则减弱了这一作用。应用Res逆转了HFS大鼠主动脉和心脏以及高糖培养的BAEC中eNOS和Cav-1表达的变化。Res刺激BAECs产生高糖抑制的NO。Caveolae抑制剂β-环糊精(β-Cyclodextrin,β-CD)对eNOS磷酸化水平的上调作用优于Res,而eNOS抑制剂NG-Nitro-77 L-arginine methyl ester,L-NAME对Cav-1表达无影响。我们的研究表明,HFS和体外高糖治疗引起内皮细胞通透性增高,Res至少涉及Cav-1/eNOS调节。
Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.
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