口服L-精氨酸对冠状动脉疾病患者肱动脉内皮功能的改善作用

Effects of oral L arginine supplementation on improving brachial endothelia function in patients with coronary artery disease

目的研究口服Ｌ精氨酸对冠心病患者肱动脉流量介导舒张功能（ＦＭＤ）的改善作用。方法采用随机、双盲、安慰剂对照、交叉试验设计，２０例患者平均６２８±９３岁，血压正常，冠状动脉造影证实存在冠状动脉疾病，分别口服Ｌ精氨酸（６７ｇ，３／ｄ）或安慰剂７天，间隔洗脱期７天；用高分辨率血管外超声测定治疗前后肱动脉ＦＭＤ和舌下含服硝酸甘油（０５ｍｇ）后肱动脉非内皮依赖性舒张，用高效液相（ＨＰＬＣ）测定治疗前后血浆Ｌ精氨酸水平的变化。结果口服Ｌ精氨酸１周后，肱动脉ＦＭＤ从１９４％±２６２％升高至６１５％±３０４％（配对ｔ检验：ｔ＝４４０，Ｐ＜０００１，２０例），血浆Ｌ精氨酸水平从８４３６±１５３８μｍｏｌ／Ｌ升高至１４３５６±２２９３μｍｏｌ／Ｌ（ｔ＝１０５０，Ｐ＜０００１，２０例）；安慰剂治疗前后肱动脉ＦＭＤ和血浆Ｌ精氨酸均无明显改变，试验过程中Ｌ精氨酸和安慰剂治疗前后肱动脉对舌下含服硝酸甘油的舒张反应性均无明显改变。结论短期口服Ｌ精氨酸可明显改善冠心病患者肱动脉ＦＭＤ，具有增强患者内皮功能的潜在临床意义。

Objective To determine the effects of short term oral supplementation with L arginine, the substrate for endothelium derived nitric oxide (EDNO) synthesis on improving brachial endothelial function in patients with coronary artery disease (CAD). Methods Twenty normotensive patients (male 12, female 8, aged 62.8±9.3 years) with clinical evidence of myocardial ischemia and angiographically proven CAD were assigned to a randomized double blind placebo controlled crossover study. Each patient received oral L arginine (6.7 g×3/d×7d) or placebo, separated by a washout period of 7 days. Brachial diameter was measured with high resolution external vascular ultrasound at rest, during reactive hyperaemia after 5 minutes of upper arm blood pressure cuff occlusion, again at rest, and after sublingual nitroglycerin (NTG, 0.5 mg). The diameter was also measured before treatment with oral L arginine or placebo and 3 hours after the last dose. Brachial endothelium dependent dilation and endothelium independent dilatation were expressed as the changes of the brachial diameter in response to reactive hyperaemia (causing flow mediated dilation, FMD) and sublingual NTG respectively. Plasma L arginine levels at baseline and 2 hours after the last dose of oral L arginine or placebo were analyzed with high performance liquid chromatography (HPLC). Results After 7 days of oral L arginine treatment, brachial FMD increased form 1 94%±2.62% to 6.15%±3.04% (paired t test: t =4.40, P <0.001, n =20), and plasma L arginine rose from 84.36±15.38 to 143.56±22.93 μmol/L ( t =10.50, P <0.001, n =20). No significant changes of brachial FMD (1.96, 2.03 vs 2.27, 2.52%, t =0.63, P =0.53, n =20) and plasma L arginine (77.72±16.79 vs 80.47±13.86 μmol/L, t =0.82, P =0.42, n =20) were observed before and after placebo. There were no significant changes of brachial dilator responses to sublingual nitroglycerin throughout the study in both L arginine and placebo groups. Conclusion These results provide evidence that short term oral supplementation with L arginine may effectively inmprove brachial FMD and may have potential clinical significance in restoring endothelial function in patients with angiographically proven CAD.