Ceylan Erkan, Aksoy Nurten, Gencer Mehmet, Vural Huseyin, Keles Huseyin, Selek Sahbettin
Department of Chest Diseases, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
Respir Med. 2005 Jul;99(7):871-6. doi: 10.1016/j.rmed.2004.12.001. Epub 2005 Jan 26.
Reactive nitrogen, oxygen species and oxidative stress are related to many pulmonary diseases. Nitric oxide (NO) may be involved in either the protection against or the induction of oxidative stress within various tissues. It is derived from the amino acid L-arginine by the action of NO synthase (NOS). L-arginine can also be metabolized by arginase with the production of ornithine and urea. Because of the competition between NOS and arginase for the same substrate, their activities are regulated reciprocally. Therefore, the rate of NO generation associated with oxidative stress is dependent on the relative activities of both NOS and arginase. The objective of this study is to investigate the L-arginine-NO pathway, evaluate oxidative-antioxidative status in the patients with asthma and demonstrate their reciprocal regulation.
30 voluntary asthmatic patients and 30 healthy control subjects with similar age range and sex were included in the study. A total of 10 ml venous blood was drawn, plasma and packed erythrocytes were prepared for the biochemical analyses. Plasma arginase activities and NO levels, and erythrocyte malondialdehyde and reduced glutathione levels were detected.
Plasma malondialdehyde levels were significantly higher and glutathione levels were lower in patients with asthma than those of the control subjects (P < 0.001 and P < 0.01, respectively). Arginase activities were significantly lower and NO levels were higher in the patients than those of the controls (P < 0.001 for both). The negative correlation between arginase and NO levels in the patients was significant (r = -0.47; P < 0.01). There was also a positive correlation between malondialdehyde and NO levels in the patients (r = 0.51; P < 0.01).
The results suggest that the L-arginine-NO pathway is involved in the pathophysiology of asthma; the arginase activities decrease which causes an increase in the L-arginine levels thereby up-regulation of NO production may contribute to the increase of oxidative stress in asthma.
活性氮、氧自由基及氧化应激与多种肺部疾病相关。一氧化氮（NO）可能参与多种组织中氧化应激的保护或诱导过程。它由一氧化氮合酶（NOS）作用于氨基酸L-精氨酸产生。L-精氨酸也可被精氨酸酶代谢生成鸟氨酸和尿素。由于NOS和精氨酸酶对同一底物存在竞争，它们的活性相互调节。因此，与氧化应激相关的NO生成速率取决于NOS和精氨酸酶的相对活性。本研究的目的是探究L-精氨酸-NO途径，评估哮喘患者的氧化-抗氧化状态，并证明它们的相互调节作用。
本研究纳入30例自愿参与的哮喘患者和30例年龄范围及性别相似的健康对照者。采集10ml静脉血，制备血浆和压积红细胞用于生化分析。检测血浆精氨酸酶活性、NO水平以及红细胞丙二醛和还原型谷胱甘肽水平。
哮喘患者血浆丙二醛水平显著高于对照组，谷胱甘肽水平低于对照组（分别为P < 0.001和P < 0.01）。患者的精氨酸酶活性显著低于对照组，NO水平高于对照组（两者均为P < 0.001）。患者中精氨酸酶与NO水平呈显著负相关（r = -0.47；P < 0.01）。患者中丙二醛与NO水平也呈正相关（r = 0.51；P < 0.01）。
结果表明L-精氨酸-NO途径参与哮喘的病理生理过程；精氨酸酶活性降低导致L-精氨酸水平升高，从而使NO生成上调，这可能导致哮喘患者氧化应激增加。
