Waring W Stephen, McKnight John A, Webb David J, Maxwell Simon R J
Clinical Pharmacology Unit, University of Edinburgh, The Queen's Medical Research Institute, 3rd Floor East, Room E3.22, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Diabetes. 2006 Nov;55(11):3127-32. doi: 10.2337/db06-0283.
Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.
内皮功能障碍是1型糖尿病患者和经常吸烟者的典型表现，也是动脉粥样硬化的重要先兆。尿酸分子具有抗氧化特性，可能会影响内皮功能。在一项随机、四组、双盲、安慰剂对照研究中，对8名1型糖尿病男性患者、8名健康常吸烟者和8名年龄匹配的健康对照者进行了急性升高尿酸浓度对内皮功能影响的研究。受试者在1小时内分不同时间接受静脉注射1000毫克尿酸加溶媒、1000毫克维生素C作为对照抗氧化剂、单独的溶媒或0.9%生理盐水。使用静脉阻断体积描记法评估前臂血流对肱动脉内乙酰胆碱和硝普钠的反应。与对照受试者相比，糖尿病患者（P < 0.００１）和吸烟者（P < 0.００５）对乙酰胆碱的反应受损，但对硝普钠的反应未受损。给予尿酸和维生素C可选择性改善1型糖尿病患者（P < 0.０１）和常吸烟者（P < 0.０５）对乙酰胆碱的反应。给予尿酸可改善1型糖尿病患者和吸烟者前臂血管床的内皮功能，这表明体内高尿酸浓度可能在这些以及其他与心血管风险增加相关的疾病中起到保护作用。
