Maestrelli P, Páska C, Saetta M, Turato G, Nowicki Y, Monti S, Formichi B, Miniati M, Fabbri L M
Dept of Environmental Medicine and Public Health, Section of Respiratory Diseases, University of Padova, Padua, Italy.
Eur Respir J. 2003 Jun;21(6):971-6. doi: 10.1183/09031936.03.00098203.
Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lung tissue was directly related to iNOS expression and associated with lower values of forced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD. In conclusion, the results suggest that the enzymes involved in the oxidative stress response may have a different role in the lung defence and that imbalance between haem oxygenase-1 and inducible nitric oxide synthase may be associated with the development of severe impairment in chronic obstructive pulmonary disease patients.
氧化/抗氧化失衡与慢性阻塞性肺疾病（COPD）的发病机制有关。本研究分别检测了重度COPD患者和无肺功能损害的对照吸烟者中抗氧化酶和促氧化酶、血红素加氧酶（HO）和诱导型一氧化氮合酶（iNOS）的表达。在肺外周定量检测HO-1、HO-2、iNOS以及以硝基酪氨酸（N-Tyr）表示的一氧化氮衍生氧化剂的免疫反应性。与对照吸烟者相比，重度COPD患者中HO-1+肺泡巨噬细胞减少，而iNOS+巨噬细胞未见差异。相反，重度患者肺泡壁中iNOS+细胞数量显著增多。这些iNOS+细胞被鉴定为Ⅱ型肺细胞，其数量与HO-1+巨噬细胞呈负相关。两组间N-Tyr免疫染色无显著差异。然而，肺组织中蛋白质硝化率与iNOS表达直接相关，并与一秒用力呼气量/用力肺活量较低值相关。HO-2由Ⅱ型肺细胞组成性表达，且在重度COPD患者中这些细胞增多。总之，结果表明参与氧化应激反应的酶在肺防御中可能具有不同作用，且血红素加氧酶-1和诱导型一氧化氮合酶之间的失衡可能与慢性阻塞性肺疾病患者严重肺功能损害的发生有关。
