Kume Hiroaki, Yamada Ryuki, Sato Yuki, Togawa Ryuichi
Department of Infectious Diseases and Respiratory Medicine, Fukushima Medical University Aizu Medical Center, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu City 969-3492, Fukushima, Japan.
Antioxidants (Basel). 2023 Jan 6;12(1):142. doi: 10.3390/antiox12010142.
Since COPD is a heterogeneous disease, a specific anti-inflammatory therapy for this disease has not been established yet. Oxidative stress is recognized as a major predisposing factor to COPD related inflammatory responses, resulting in pathological features of small airway fibrosis and emphysema. However, little is known about effects of oxidative stress on airway smooth muscle. Cigarette smoke increases intracellular Ca concentration and enhances response to muscarinic agonists in human airway smooth muscle. Cigarette smoke also enhances proliferation of these cells with altered mitochondrial protein. Hydrogen peroxide and 8-isoprostans are increased in the exhaled breath condensate in COPD. These endogenous oxidants cause contraction of tracheal smooth muscle with Ca dynamics through Ca channels and with Ca sensitization through Rho-kinase. TNF-α and growth factors potentiate proliferation of these cells by synthesis of ROS. Oxidative stress can alter the function of airway smooth muscle through Ca signaling. These phenotype changes are associated with manifestations (dyspnea, wheezing) and pathophysiology (airflow limitation, airway remodeling, airway hyperresponsiveness). Therefore, airway smooth muscle is a therapeutic target against COPD; oxidative stress should be included in treatable traits for COPD to advance precision medicine. Research into Ca signaling related to ROS may contribute to the development of a novel agent for COPD.
由于慢性阻塞性肺疾病（COPD）是一种异质性疾病，目前尚未确立针对该疾病的特异性抗炎治疗方法。氧化应激被认为是COPD相关炎症反应的主要诱发因素，会导致小气道纤维化和肺气肿的病理特征。然而，关于氧化应激对气道平滑肌的影响却知之甚少。香烟烟雾会增加人气道平滑肌细胞内的钙离子浓度，并增强其对毒蕈碱激动剂的反应。香烟烟雾还会通过改变线粒体蛋白来增强这些细胞的增殖。慢性阻塞性肺疾病患者呼出的呼出气冷凝物中过氧化氢和8-异前列腺素含量增加。这些内源性氧化剂通过钙通道引起气管平滑肌收缩，并通过Rho激酶使钙离子致敏。肿瘤坏死因子-α（TNF-α）和生长因子通过活性氧（ROS）的合成增强这些细胞的增殖。氧化应激可通过钙信号改变气道平滑肌的功能。这些表型变化与临床表现（呼吸困难、喘息）和病理生理学（气流受限、气道重塑、气道高反应性）相关。因此，气道平滑肌是治疗慢性阻塞性肺疾病的一个靶点；氧化应激应纳入慢性阻塞性肺疾病的可治疗特征中，以推动精准医学的发展。对与活性氧相关的钙信号的研究可能有助于开发一种治疗慢性阻塞性肺疾病的新型药物。
