NO暴露对哮喘小鼠气道炎症和氧化应激的影响
2023/09/21
摘要
背景：一氧化氮（NO）是一种广泛存在于空气的污染物。流行病学证据表明，NO与哮喘发病率和死亡率增加有关，但其机制尚不清楚。
方法：在这项研究中，我们间歇性地将小鼠暴露于NO中（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4组：生理盐水对照组，卵清蛋白（OVA）致敏组，单独NO组和OVA+NO组。从气道炎症和氧化应激的角度发现了相关的机制。
结果：结果显示，NO暴露可加重哮喘小鼠肺部炎症反应，气道重塑的特征是气道壁明显增厚，炎症细胞浸润。此外，NO会加重气道高反应性（AHR），其特征是吸气阻力（Ri）和呼气阻力（Re）显着升高，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升高，IFN-γ降低，IL-4/IFN-γ显着升高），在NO暴露下哮喘炎症反应中起关键作用。
结论：简而言之，NO暴露可促进过敏性气道炎症并增加哮喘易感性。暴露于NO的哮喘小鼠中ROS和MDA水平显着增加，而GSH水平急剧下降。这些发现可能为NO暴露引起的过敏性哮喘风险机制提供更好的毒理学证据。
Lu C, Wang F, Liu Q
Abstrast
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
背景：一氧化氮（NO）是一种广泛存在于空气的污染物。流行病学证据表明，NO与哮喘发病率和死亡率增加有关，但其机制尚不清楚。
方法：在这项研究中，我们间歇性地将小鼠暴露于NO中（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4组：生理盐水对照组，卵清蛋白（OVA）致敏组，单独NO组和OVA+NO组。从气道炎症和氧化应激的角度发现了相关的机制。
结果：结果显示，NO暴露可加重哮喘小鼠肺部炎症反应，气道重塑的特征是气道壁明显增厚，炎症细胞浸润。此外，NO会加重气道高反应性（AHR），其特征是吸气阻力（Ri）和呼气阻力（Re）显着升高，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升高，IFN-γ降低，IL-4/IFN-γ显着升高），在NO暴露下哮喘炎症反应中起关键作用。
结论：简而言之，NO暴露可促进过敏性气道炎症并增加哮喘易感性。暴露于NO的哮喘小鼠中ROS和MDA水平显着增加，而GSH水平急剧下降。这些发现可能为NO暴露引起的过敏性哮喘风险机制提供更好的毒理学证据。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Hazard Mater 2023 Sep 05;457;doi: 10.1016/j.jhazmat.2023.131787. IF：9.038.)
Effect of NO exposure on airway inflammation and oxidative stress in asthmatic mice.(J Hazard Mater 2023 Sep 05;457;doi: 10.1016/j.jhazmat.2023.131787. IF：9.038.)
Lu C, Wang F, Liu Q
Abstrast
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
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支气管热成形术诱导重症哮喘气道壁细胞外基质的变化
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