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血管功能障碍与慢性阻塞性肺疾病:氧化还原平衡的作用。

Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox balance.

机构信息

VA Medical Center Bldg 2, Rm 1D25, 500 Foothill Dr, Salt Lake City, UT 84148.

出版信息

Hypertension. 2014 Mar;63(3):459-67. doi: 10.1161/HYPERTENSIONAHA.113.02255. Epub 2013 Dec 9.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 versus 4.7±0.6%; P<0.05; placebo versus antioxidant cocktail), but not controls (6.7±0.6 versus 6.9±0.7%; P>0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s(-1); P<0.05; placebo versus antioxidant cocktail) while not affecting controls (11±2 versus 10±1 m·s(-1); P>0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population's greater risk and incidence of cardiovascular disease.

摘要

慢性阻塞性肺疾病(COPD)的特征是肺功能降低、炎症、自由基生成、血管功能障碍,随后心血管疾病的发病率更高。我们通过给 COPD 患者(n=30)和对照组(n=30)口服急性抗氧化鸡尾酒,来研究氧化还原平衡在这些患者血管功能障碍中的作用。采用双盲、随机、安慰剂对照、交叉设计,COPD 患者和对照组在口服安慰剂或抗氧化鸡尾酒(维生素 C、维生素 E、α-硫辛酸)后,使用超声多普勒评估肱动脉血流介导的扩张和颈动脉-桡动脉脉搏波速度。与对照组相比,患者的基线抗氧化水平(维生素 C 和超氧化物歧化酶活性)较低,氧化应激水平(硫代巴比妥酸反应性物质)较高。患者的基础血流介导扩张也较低(P<0.05),但抗氧化鸡尾酒显著改善了该指标(3.1±0.5 对 4.7±0.6%;P<0.05;安慰剂对抗氧化鸡尾酒),但对照组没有改善(6.7±0.6 对 6.9±0.7%;P>0.05;安慰剂对抗氧化鸡尾酒)。抗氧化鸡尾酒还改善了 COPD 患者的脉搏波速度(14±1 对 11±1 m·s(-1);P<0.05;安慰剂对抗氧化鸡尾酒),而对对照组没有影响(11±2 对 10±1 m·s(-1);P>0.05;安慰剂对抗氧化鸡尾酒)。COPD 患者表现出血管功能障碍,可能是由氧化还原平衡改变介导的,这种改变可以通过口服抗氧化剂来急性缓解。因此,自由基介导的血管功能障碍可能是导致该人群心血管疾病风险和发病率更高的重要机制。

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