Hayashi Toshio, Juliet Packiasamy A R, Matsui-Hirai Hisako, Miyazaki Asaka, Fukatsu Akiko, Funami Jun, Iguchi Akihisa, Ignarro Louis J
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13681-6. doi: 10.1073/pnas.0506595102. Epub 2005 Sep 12.
The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma NO(2)(-)+NO(3)(-) and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.
本研究的目的是评估摄入的左旋精氨酸、左旋瓜氨酸和抗氧化剂（维生素C和E）对喂食高胆固醇饮食的家兔动脉粥样硬化进展的影响。高脂饮食导致离体胸主动脉中内皮依赖性血管舒张功能显著受损，以及家兔耳动脉体内血流受损，导致胸主动脉出现动脉粥样硬化病变并增加超氧阴离子生成，同时增加氧化敏感基因[Elk-1和磷酸化的cAMP反应元件结合蛋白]的表达。家兔口服左旋精氨酸、左旋瓜氨酸和/或抗氧化剂治疗12周。左旋精氨酸加左旋瓜氨酸，单独使用或与抗氧化剂联合使用，均可显著改善内皮依赖性血管舒张功能和血流，使动脉粥样硬化病变显著消退，并减少超氧阴离子生成和氧化敏感基因表达。这些治疗效果与主动脉内皮型一氧化氮合酶表达以及血浆NO(2)(-)+NO(3)(-)和cGMP水平的同时升高有关。这些观察结果表明，摄入某些一氧化氮增强物质，包括左旋精氨酸、左旋瓜氨酸和抗氧化剂，可以消除氧化应激状态并逆转动脉粥样硬化的进展。这种方法可能在人类动脉粥样硬化的治疗中具有临床应用价值。
