XiangYa School of Public Health, Central South University, Changsha 410078, China.
Division of Animal and Human Health Engineering, Department of Biosystems, KU Leuven, Leuven 3001, Belgium.
J Hazard Mater. 2023 Sep 5;457:131787. doi: 10.1016/j.jhazmat.2023.131787. Epub 2023 Jun 7.
Nitrogen dioxide (NO) is a widespread air pollutant. Epidemiological evidence indicates that NO is associated with an increase of incidence rate and mortality of asthma, but its mechanism is still unclear. In this study, we exposed mice to NO (5 ppm, 4 h per day for 30 days) intermittently to investigate the development and potential toxicological mechanisms of allergic asthma. We randomly assigned 60 male Balb/c mice to four groups: saline control, ovalbumin (OVA) sensitization, NO alone, and OVA+NO groups. The involved mechanisms were found from the perspective of airway inflammation and oxidative stress. The results showed that NO exposure could aggravate lung inflammation in asthmatic mice, and airway remodeling was characterized by significant thickening of the airway wall and infiltration of inflammatory cells. Moreover, NO would aggravate the airway hyperresponsiveness (AHR), which is characterized by significantly elevated inspiratory resistance (Ri) and expiratory resistance (Re), as well as decreased dynamic lung compliance (Cldyn). In addition, NO exposure promoted pro-inflammatory cytokines (IL-6 and TNF-α) and serum immunoglobulin (IgE) production. The imbalance of Th1/Th2 cell differentiation (IL-4 increased, IFN-γ reduced, IL-4/IFN-γ significantly increased) played a key role in the inflammatory response of asthma under NO exposure. In a nutshell, NO exposure could promote allergic airway inflammation and increase asthma susceptibility. The levels of ROS and MDA among asthmatic mice exposed to NO increased significantly, while GSH levels sharply decreased. These findings may provide better toxicological evidence for the mechanisms of allergic asthma risk due to NO exposure.
二氧化氮（NO）是一种广泛存在的空气污染物。流行病学证据表明，NO 与哮喘发病率和死亡率的增加有关，但其机制尚不清楚。在这项研究中，我们让小鼠间歇性暴露于 NO（5ppm，每天 4 小时，持续 30 天），以研究过敏性哮喘的发展和潜在的毒理学机制。我们将 60 只雄性 Balb/c 小鼠随机分为四组：生理盐水对照组、卵清蛋白（OVA）致敏组、NO 单独组和 OVA+NO 组。从气道炎症和氧化应激的角度探讨了所涉及的机制。结果表明，NO 暴露可加重哮喘小鼠的肺部炎症，气道重塑的特征是气道壁显著增厚和炎症细胞浸润。此外，NO 会加重气道高反应性（AHR），表现为吸气阻力（Ri）和呼气阻力（Re）显著升高，以及动态肺顺应性（Cldyn）降低。此外，NO 暴露促进促炎细胞因子（IL-6 和 TNF-α）和血清免疫球蛋白（IgE）的产生。Th1/Th2 细胞分化失衡（IL-4 增加，IFN-γ 减少，IL-4/IFN-γ 显著增加）在 NO 暴露下的哮喘炎症反应中发挥关键作用。简而言之，NO 暴露可促进过敏性气道炎症，增加哮喘易感性。暴露于 NO 的哮喘小鼠的 ROS 和 MDA 水平显著升高，而 GSH 水平急剧下降。这些发现可能为 NO 暴露导致过敏性哮喘风险的机制提供更好的毒理学证据。
