Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
J Atheroscler Thromb. 2010 Feb 26;17(2):173-80. doi: 10.5551/jat.2378. Epub 2010 Feb 12.
Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia.
Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment.
Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels.
Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.
依折麦布是一种尼曼-匹克 C1 样蛋白 1 抑制剂，已被证明可减少胆固醇的肠道吸收。我们研究了它是否对高胆固醇血症患者的代谢紊乱和/或肾功能不全也有有益作用。
依折麦布被给予 38 名日本高胆固醇血症患者以获得适当的低密度脂蛋白胆固醇（LDL-chol）水平。年龄和性别匹配的高胆固醇血症患者（n=38）为对照组。我们评估了依折麦布治疗前和治疗后 4 至 8 周的效果。
依折麦布显著降低 LDL-chol 水平和代谢综合征相关因素，包括体重、腰围、血压；稳态模型评估胰岛素抵抗（HOMA-IR）和尿白蛋白排泄均显著降低。此外，它降低了高敏 C 反应蛋白（hs-CRP）、肿瘤坏死因子（TNF）-α、氧化应激参数 8-羟基-2'-脱氧鸟苷的尿排泄量，并增加了硝酸盐和亚硝酸盐（NOx）的尿排泄量。在对照组中我们没有观察到这种变化。除了血清 TNF-α水平下降外，依折麦布的作用与 LDL-chol 水平的降低无关。
依折麦布改善了代谢综合征和微量白蛋白尿的状况，减少了炎症和氧化应激，并增加了一氧化氮的生物利用度，这与 LDL-chol 的降低依赖和独立的方式有关。
