Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands.
J Nutr Biochem. 2013 Aug;24(8):1423-30. doi: 10.1016/j.jnutbio.2012.11.009. Epub 2013 Jan 18.
Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (-52%) in the aortic root, comparable to atorvastatin (-40%) and the combination of both drugs (-47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (-19%) comparable to atorvastatin (-19%) and the combination (-22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.
白藜芦醇是传统亚洲草药和红酒中的主要成分，由于其具有降低血脂、抗炎和抗氧化作用，被认为是一种有潜力的抗动脉粥样硬化药物。本研究旨在评估白藜芦醇是否能预防 APOE*3-Leiden.CETP（E3L.CETP）小鼠的动脉粥样硬化发展，并增强目前应用最广泛的抗动脉粥样硬化疗法——温和他汀类药物治疗的抗动脉粥样硬化作用。E3L.CETP 小鼠喂食富含胆固醇的饮食，同时给予（对照组）或不给予白藜芦醇（0.01%w/w）、阿托伐他汀（0.0027%w/w）或两者联合治疗 14 周。在研究过程中，测定了血浆脂质、炎症和氧化应激参数。白藜芦醇可减少主动脉根部的动脉粥样硬化病变面积（-52%），与阿托伐他汀（-40%）和两种药物的联合治疗（-47%）相当。动脉粥样硬化病变中的胶原/巨噬细胞比值是斑块稳定性的标志物，白藜芦醇（+108%）、阿托伐他汀（+124%）和两种药物的联合治疗（+154%）均能增加该比值。白藜芦醇可降低血浆胆固醇水平（-19%），与阿托伐他汀（-19%）和两种药物的联合治疗（-22%）相当，且这种作用完全局限于各组的（非常）低密度脂蛋白胆固醇水平。事后分析表明，阿托伐他汀的抗动脉粥样硬化作用可以通过降低胆固醇来解释，而白藜芦醇的抗动脉粥样硬化作用可能归因于除降低胆固醇之外的因素。炎症和氧化应激标志物没有差异，但白藜芦醇可改善巨噬细胞功能。综上，白藜芦醇可强力降低 E3L.CETP 小鼠的动脉粥样硬化发展，并诱导更稳定的病变表型。然而，在本实验条件下，白藜芦醇并未增强阿托伐他汀的抗动脉粥样硬化作用。
