Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice: A critical role of NADPH oxidase
Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice: A critical role of NADPH oxidase
复制标题
槲皮素可减轻载脂蛋白 E 敲除小鼠中高脂肪饮食引起的动脉粥样硬化：NADPH 氧化酶的关键作用
DOI：
10.1016/j.fct.2017.03.048
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发表时间：
2017
影响因子：
4.3
通讯作者：
Yao Ping
中科院分区：
文献类型：
--
作者：
Xiao Lin;Liu Liang;Guo Xiaoping;Zhang Shanshan;Wang Jing;Zhou Feng;Liu Liegang;Tang Yuhan;Yao Ping
活性氧（ROS）已成为心血管功能的重要分子。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是吞噬细胞和血管细胞中活性氧的主要来源。一些证据表明槲皮素有助于预防动脉粥样硬化。本研究在体内研究槲皮素通过调节NADPH氧化酶亚基表达减轻动脉粥样硬化的作用，并探讨槲皮素抑制ox-LDL刺激小鼠腹腔巨噬细胞（MPMs） ROS过量产生的机制。ApoE KO模型小鼠分别饲喂正常饲料和高脂饲料（HFD），并添加或不添加槲皮素，持续24周。与HFD组相比，槲皮素显著减少动脉粥样硬化斑块面积，减轻系统性氧化应激，抑制主动脉p47phox、p67phox表达，部分逆转NOX4表达。槲皮素在体外有效抑制ox-LDL诱导的MPMs中ROS的形成，阻断NADPH氧化酶激活的关键步骤- p47phox的膜易位。我们的研究结果表明，经常食用槲皮素对NADPH氧化酶亚基有明显的调节作用，可以预防动脉粥样硬化。
Reactive oxygen species (ROS) have emerged as important molecules in cardiovascular function. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in phagocytic and vascular cells. Several lines of evidence indicate that quercetin contributes to protecting against atherosclerosis. Herein, we investigated the effect of quercetin on alleviating atherosclerosis by regulating NADPH oxidase subunits expression in vivo, and explored the mechanism of quercetin suppressing the ROS overproduction stimulated by ox-LDL in mouse peritoneal macrophages (MPMs). Model ApoE KO mice were fed with either a normal chow diet or a high fat diet (HFD) supplemented with or without dosed quercetin for 24 weeks. Quercetin significantly reduced the atherosclerotic plaque area, alleviated the systemic oxidative stress, and suppressed aortic p47phox, p67phox expressions but partially reversed the NOX4 expression as compared to those in the HFD group. In vitro, quercetin effectively inhibited the ox-LDL induced ROS formation in MPMs, and blocked the vital step in activation of NADPH oxidase — membrane translocation of p47phox. Our findings suggest that regular consumption of dietary quercetin plays a role in preventing atherosclerosis giving its evident regulatory effect on subunits of NADPH oxidase.