Hanazawa T, Kharitonov S A, Barnes P J
Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1273-6. doi: 10.1164/ajrccm.162.4.9912064.
The reaction of nitric oxide (NO) and superoxide anions (O(2)(-)) in the airway results in the formation of peroxynitrite, a highly reactive oxidant species. Peroxynitrite reacts with tyrosine residues in proteins to form the stable product nitrotyrosine. We investigated whether nitrotyrosine in exhaled breath condensates may be increased in patients with asthma. Four groups of nonsmoking subjects were studied. We measured exhaled NO, nitrotyrosine, and leukotrienes concentrations in breath condensate in healthy nonatopic subjects (n = 15) and in patients with mild asthma (steroid naive, n = 15), moderate asthma (inhaled steroid treatment, n = 12), and severe asthma (oral steroid treatment, n = 12). Exhaled NO was increased significantly in patients with mild (19.2 +/- 2.7 ppb, p < 0.01) and moderate asthma (14.0 +/- 1.53 ppb, p < 0.05), as compared with normal control (6.58 +/- 0.61 ppb). The levels of LTC(4)/D(4)/E(4) and LTB(4) were increased significantly in patients with moderate and severe asthma treated with steroids. Nitrotyrosine concentrations were detectable (6.3 +/- 0.8 ng/ml) in breath condensate of normal subjects, and were increased significantly in patients with mild asthma (15.3 +/- 2.0 ng/ml, p < 0.01). However, the levels of nitrotyrosine in exhaled condensate were lower in patients with moderate (5.0 +/- 0.6 ng/ml) and severe asthma (3.3 +/- 0.6 ng/ml, p < 0.05). There was a significant correlation between nitrotyrosine in breath condensate and exhaled NO in patients with mild asthma (r = 0.65, p < 0.05). We conclude that nitrotyrosine formation in exhaled breath condensates may be a marker of oxidative stress in airways of asthma.
气道中一氧化氮(NO)与超氧阴离子(O₂⁻)反应会生成过氧亚硝酸盐,这是一种高活性氧化物质。过氧亚硝酸盐与蛋白质中的酪氨酸残基反应形成稳定产物硝基酪氨酸。我们研究了哮喘患者呼出气冷凝物中的硝基酪氨酸水平是否会升高。我们对四组不吸烟受试者进行了研究。我们测量了健康非特应性受试者(n = 15)、轻度哮喘患者(未使用类固醇,n = 15)、中度哮喘患者(吸入类固醇治疗,n = 12)和重度哮喘患者(口服类固醇治疗,n = 12)呼出气冷凝物中的呼出气NO、硝基酪氨酸和白三烯浓度。与正常对照组(6.58 ± 0.61 ppb)相比,轻度哮喘患者(19.2 ± 2.7 ppb,p < 0.01)和中度哮喘患者(14.0 ± 1.53 ppb,p < 0.05)的呼出气NO显著升高。接受类固醇治疗的中度和重度哮喘患者的LTC₄/D₄/E₄和LTB₄水平显著升高。正常受试者的呼出气冷凝物中可检测到硝基酪氨酸浓度(6.3 ± 0.8 ng/ml),轻度哮喘患者的硝基酪氨酸浓度显著升高(15.3 ± 2.0 ng/ml,p < 0.01)。然而,中度哮喘患者(5.0 ± 0.6 ng/ml)和重度哮喘患者(3.3 ± 0.6 ng/ml,p < 0.05)的呼出气冷凝物中硝基酪氨酸水平较低。轻度哮喘患者的呼出气冷凝物中的硝基酪氨酸与呼出气NO之间存在显著相关性(r = 0.65,p < 0.05)。我们得出结论,呼出气冷凝物中硝基酪氨酸的形成可能是哮喘气道氧化应激的一个标志物。