Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Ann Med. 1995 Jun;27(3):389-93. doi: 10.3109/07853899509002592.
Nitric oxide (NO) may play an important role in regulating airway function and in the pathophysiology of inflammatory airway diseases. Endothelium-derived NO may be important in regulating airway blood flow and, indirectly, plasma exudation. NO is the neurotransmitter of bronchodilator nerves in human airways and counteracts the bronchoconstriction due to cholinergic neural mechanisms. Inducible NO synthase (iNOS) is expressed in human epithelial cells in response to pro-inflammatory cytokines and oxidants, probably via activation of the transcription factor nuclear factor kappa B (NF-kappa B). There is increased expression of iNOS in the epithelium of asthmatic patients and in lung macrophages in bronchiectasis. This may account for the increased concentration of NO in the exhaled air of patients with inflammatory airways disease. Increased NO production in the airways may result in hyperaemia, plasma exudation, mucus secretion and indirectly increased proliferation of Th2 lymphocytes responsible for eosinophilic inflammation. Glucocorticoids inhibit the induction of iNOS in epithelial cells and reduce the elevated exhaled NO to normal values. Selective inhibitors of iNOS may be useful in the treatment of inflammatory airway diseases, such as asthma, in the future.
一氧化氮（NO）可能在调节气道功能以及炎性气道疾病的病理生理学过程中发挥重要作用。内皮源性NO可能在调节气道血流以及间接调节血浆渗出方面具有重要作用。NO是人类气道中舒张支气管神经的神经递质，可对抗胆碱能神经机制引起的支气管收缩。诱导型一氧化氮合酶（iNOS）在人类上皮细胞中响应促炎细胞因子和氧化剂而表达，可能是通过激活转录因子核因子κB（NF-κB）实现的。哮喘患者的上皮以及支气管扩张症患者的肺巨噬细胞中iNOS表达增加。这可能解释了炎性气道疾病患者呼出气中NO浓度升高的原因。气道中NO生成增加可能导致充血、血浆渗出、黏液分泌，并间接导致负责嗜酸性粒细胞炎症的Th2淋巴细胞增殖增加。糖皮质激素可抑制上皮细胞中iNOS的诱导，并将升高的呼出气NO降低至正常水平。iNOS的选择性抑制剂未来可能在治疗炎性气道疾病（如哮喘）中发挥作用。
