Dworski R, Roberts L J, Murray J J, Morrow J D, Hartert T V, Sheller J R
Department of Critical Care Medicine, Vanderbilt University School of Medicine, T-1217 MCN, Nashville, TN 37232-2650, USA.
Clin Exp Allergy. 2001 Mar;31(3):387-90. doi: 10.1046/j.1365-2222.2001.01055.x.
Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F2-isoprostanes (F2-IsoPs), free radical-catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoP-M), the major urinary metabolite of the F2-IsoP, 15-F2t-IsoP (8-iso-PGF2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F2-IsoPs in urine and plasma. To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15-F2t-IsoP-M. Analysis of 15-F2t-IsoP-M by GC-NICI-MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine. Urinary excretion of 15-F2t-IsoP-M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8-h period of the study compared to the baseline value (ANOVA, and Student-Newman-Keuls multiple comparisons test). No increase in the urinary excretion of 15-F2t-IsoP-M occurred after inhalation of methacholine. Allergen challenge causes an oxidant injury in human atopic asthmatics. 15-F2t-IsoP-M is a valuable marker of oxidant stress in vivo.
哮喘是一种气道慢性炎症性疾病，可能涉及肺部的氧化损伤。体内氧化应激的评估较为困难，但测量F2 -异前列腺素（F2 - IsoPs），即花生四烯酸的自由基催化产物，似乎为体内氧化应激状态的定量测量提供了一种可靠的方法。我们最近开发了一种用于检测2,3 -二去甲-5,6 -二氢-15 - F2t -异前列腺素（15 - F2t - IsoP - M）的质谱分析法，15 - F2t - IsoP - M是F2 - IsoP（8 -异前列环素F2α）的主要尿代谢产物。测量这种代谢产物的尿排泄量可提供体内氧化应激状态的可靠指标，相较于测量尿液和血浆中未代谢的F2 - IsoPs具有优势。通过测量15 - F2t - IsoP - M的尿排泄量来评估特应性哮喘患者在体内接触过敏原后氧化应激的发生情况。采用气相色谱-负离子化学电离质谱法（GC - NICI - MS）分析9名轻度特应性哮喘患者吸入过敏原激发后以及4名哮喘受试者吸入乙酰甲胆碱激发后的15 - F2t - IsoP - M。与基线值相比，过敏原激发后2小时，15 - F2t - IsoP - M的尿排泄量增加，且在随后研究的8小时内所有尿液样本中均显著升高（方差分析和Student - Newman - Keuls多重比较检验）。吸入乙酰甲胆碱后，15 - F2t - IsoP - M的尿排泄量未增加。过敏原激发会导致人类特应性哮喘患者发生氧化损伤。15 - F2t - IsoP - M是体内氧化应激的一个有价值的标志物。
