高残留脂蛋白水平患者使用α-生育酚治疗改善内皮血管舒缩功能障碍。

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.

作者信息

Kugiyama K, Motoyama T, Doi H, Kawano H, Hirai N, Soejima H, Miyao Y, Takazoe K, Moriyama Y, Mizuno Y, Tsunoda R, Ogawa H, Sakamoto T, Sugiyama S, Yasue H

机构信息

Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto City, Japan.

出版信息

J Am Coll Cardiol. 1999 May;33(6):1512-8. doi: 10.1016/s0735-1097(99)00057-1.

DOI:10.1016/s0735-1097(99)00057-1

PMID:10334416

Abstract

OBJECTIVES

This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels.

BACKGROUND

Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis.

METHODS

Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients).

RESULTS

Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.4% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05).

CONCLUSIONS

Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction, in patients with high remnants levels.

摘要

目的

本研究旨在探讨口服抗氧化剂α-生育酚是否能改善高残留脂蛋白水平患者的内皮依赖性血管舒张功能。

背景

已知残留脂蛋白具有致动脉粥样硬化作用，并损害内皮依赖性动脉舒张功能，但其潜在机制仍不清楚。氧化应激是动脉粥样硬化各种危险因素的共同特征。

方法

采用高分辨率超声技术，在40例空腹状态下血清残留脂蛋白水平高（分别>150例连续住院患者残留脂蛋白水平分布的第75百分位数）和30例残留脂蛋白水平低（<第25百分位数）的患者中，随机给予口服α-生育酚醋酸酯（300 IU/天）或安慰剂治疗4周，治疗前后检测反应性充血期间肱动脉的血流介导的血管舒张功能。

结果

治疗前，高残留脂蛋白水平患者的血流介导的血管舒张功能低于低残留脂蛋白水平患者（4.1±0.3%对6.0±0.5%，p<0.01）。α-生育酚治疗而非安慰剂治疗显著增加了高残留脂蛋白水平患者的血流介导的血管舒张功能（α-生育酚治疗后为7.5±0.4%，安慰剂治疗后为4.2±0.4%，p<0.01）。在低残留脂蛋白水平患者中，α-生育酚无效。α-生育酚对高残留脂蛋白水平患者的有益作用与血浆中硫代巴比妥酸反应性物质水平降低有关，硫代巴比妥酸反应性物质是脂质过氧化的指标（α-生育酚治疗前为6.6±0.3 nmol/ml，α-生育酚治疗后为4.6±0.3，p<0.05）。