Wang Fei, Liu Zhen, Li Wen-Xuan, Wang Xiao-Ming, Yang Ju, Zhao Zhu-Hui, Jie Zhi-Jun
Department of Pediatrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 29. doi: 10.1007/s00210-025-03831-7.
Asthma, a widespread chronic inflammatory disease can contribute to different degrees of lung function damage. The objective of this study is to explore the potential effects of nitric oxide synthase (NOS) inhibitors in asthma using mice model induced by ovalbumin (OVA). BALB/c mice were treated with OVA to establish an asthma model. Mice were intranasally challenged with different NOS inhibitors and analyzed the impact of NOS inhibitors on the lung tissues and bronchoalveolar lavage fluid (BALF). Histopathological analysis was performed by Periodic Acid-Schiff (PAS) staining. Airway reactivity was assessed using methacholine challenge testing. The concentrations of nitric oxide (NO), Neutrophil extracellular traps (NETs), and cytokines were determined by enzyme-linked immunosorbent assay (ELISA) assay. NOS inhibitors effectively improved airway inflammation and reduced airway hyperresponsiveness. In addition, NOS inhibitors decreased the concentrations of NO, NETs, and inflammation in the airway and BALF. The decreased NO production and reduced NET formation in the lung indicate that NOS inhibitors inhibit the process of NET release to alleviate asthma.
哮喘是一种广泛存在的慢性炎症性疾病，可导致不同程度的肺功能损害。本研究的目的是利用卵清蛋白（OVA）诱导的小鼠模型，探讨一氧化氮合酶（NOS）抑制剂对哮喘的潜在影响。用OVA处理BALB/c小鼠以建立哮喘模型。用不同的NOS抑制剂对小鼠进行鼻内攻击，并分析NOS抑制剂对肺组织和支气管肺泡灌洗液（BALF）的影响。采用过碘酸希夫（PAS）染色进行组织病理学分析。使用乙酰甲胆碱激发试验评估气道反应性。通过酶联免疫吸附测定（ELISA）法测定一氧化氮（NO）、中性粒细胞胞外陷阱（NETs）和细胞因子的浓度。NOS抑制剂有效改善气道炎症并降低气道高反应性。此外，NOS抑制剂降低了气道和BALF中NO、NETs的浓度以及炎症反应。肺中NO生成减少和NET形成减少表明NOS抑制剂抑制NET释放过程以减轻哮喘。
