Staprans Ilona, Pan Xian-Mang, Rapp Joseph H, Moser Arthur H, Feingold Kenneth R
Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, USA.
J Lipid Res. 2006 Nov;47(11):2575-80. doi: 10.1194/jlr.M600261-JLR200. Epub 2006 Aug 7.
Oxidized cholesterol is present in significant quantities in the typical Western diet. When ingested, oxidized cholesterol is absorbed by the small intestine and incorporated into both chylomicrons and LDL, resulting in LDL that is more susceptible to further oxidation. Feeding studies in animal models and epidemiological studies in humans have suggested that oxidized cholesterol in the diet increases the development of atherosclerosis. In this study, we determined the effect of ezetimibe, a drug that inhibits small intestinal absorption of cholesterol, on the levels of oxidized cholesterol in the serum after a test meal containing oxidized cholesterol. We demonstrate that ezetimibe, 10 mg per day for 1 month, markedly reduced the levels (50% decrease) of oxidized cholesterol in the serum after feeding a test meal containing either alpha-epoxy cholesterol or 7-keto cholesterol, two of the predominant oxidized cholesterols found in the diet. Moreover, the decrease in oxidized cholesterol in the serum was attributable to a decrease in the incorporation of dietary oxidized cholesterol into both chylomicrons and LDL. Because there was no decrease in postprandial triglyceride levels, we conclude that this decrease in oxidized cholesterol levels in the serum is attributable to decreased absorption and not to enhanced clearance. Whether this decrease in oxidized cholesterol absorption prevents or delays the development of atherosclerosis remains to be determined.
氧化型胆固醇在典型的西方饮食中大量存在。摄入后，氧化型胆固醇被小肠吸收并整合到乳糜微粒和低密度脂蛋白（LDL）中，导致LDL更容易进一步氧化。动物模型的喂养研究和人类的流行病学研究表明，饮食中的氧化型胆固醇会增加动脉粥样硬化的发生。在本研究中，我们测定了依泽替米贝（一种抑制小肠胆固醇吸收的药物）对含氧化型胆固醇的试验餐后血清中氧化型胆固醇水平的影响。我们证明，每天服用10毫克依泽替米贝，持续1个月，在喂食含有α-环氧胆固醇或7-酮胆固醇（饮食中发现的两种主要氧化型胆固醇）的试验餐后，血清中氧化型胆固醇水平显著降低（降低50%）。此外，血清中氧化型胆固醇的降低归因于饮食中氧化型胆固醇整合到乳糜微粒和LDL中的减少。由于餐后甘油三酯水平没有降低，我们得出结论，血清中氧化型胆固醇水平的降低归因于吸收减少而非清除增强。这种氧化型胆固醇吸收的减少是否能预防或延缓动脉粥样硬化的发生还有待确定。
