Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression
Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression
复制标题
姜黄素通过抑制 Toll 样受体 4 表达减轻载脂蛋白 E 敲除小鼠的动脉粥样硬化
DOI：
10.1021/acs.jafc.7b04260
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发表时间：
2018-01-17
影响因子：
6.1
通讯作者：
Feng, Dan
中科院分区：
文献类型：
--
作者：
Zhang, Shanshan;Zou, Jun;Feng, Dan
Toll样受体4（TLR 4）在动脉粥样硬化的发病机制中起重要作用，本研究旨在探讨姜黄素是否通过抑制TLR 4的表达来抑制ApoE基因敲除（ApoE（-/-））小鼠动脉粥样硬化的发生。ApoE（-/-）小鼠喂食补充或不补充姜黄素（0.1%w/w）的高脂肪饮食16周。姜黄素补充显著降低动脉粥样硬化斑块中TLR 4表达和巨噬细胞浸润。姜黄素还降低了主动脉白细胞介素-β（IL-1 β）、肿瘤坏死因子-α（TNF-α）、血管细胞粘附分子1（VCAM-1）和细胞间粘附分子1（ICAM-1）的表达、核因子-κ B（NF-κ B）活性以及血浆IL-β、TNF-α、可溶性VCAM-1和ICAM-1水平。此外，主动脉窦切片显示姜黄素治疗降低了动脉粥样硬化病变的程度，并抑制了动脉粥样硬化的发展。在体外，姜黄素抑制NF-κ B B活化;巨噬细胞。降低脂多糖诱导的TLR 4表达。我们的研究结果表明，姜黄素至少部分通过抑制TLR 4表达及其相关的炎症反应来预防动脉粥样硬化。
Toll-like receptor 4 (TLR4) has been reported to play a critical role in the pathogenesis of atherosclerosis, the current study aimed to investigate whether curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE(-/-)) mice by inhibiting TLR4 expression. ApoE(-/-) mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques. Curcumin also reduced aortic interleukin-beta (IL-1 beta) tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear factor-kappa B (NF-kappa B) activity, and plasma IL-beta, TNF-alpha, soluble VCAM-1 and ICAM-1 levels.. In addition, aortic sinus sections revealed that curcumin treatment reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. In vitro, curcumin inhibited NF-kappa B activation in;macrophages. and reduced TLR4 expression induced by lipopolysaccharide. Our results indicate that curcumin protects against atherosclerosis at least partially by inhibiting TLR4 expression and its related inflammatory reaction.