Oxidative stress in pathogenesis of chronic obstructive pulmonary disease
Oxidative stress in pathogenesis of chronic obstructive pulmonary disease
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DOI：
10.1385/cbb:43:1:167
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发表时间：
2005-01-01
影响因子：
2.6
通讯作者：
Rahman, I
中科院分区：
文献类型：
--
作者：
Rahman, I
慢性阻塞性肺疾病（COPD）是一种缓慢进展的疾病，其特征是气流受限，这在很大程度上是不可逆的。氧化应激和炎症是COPD的主要标志。活性氧直接或通过脂质过氧化产物如4-羟基-2-壬烯醛和F-2-异前列烷的形成，可能通过活化和磷酸化丝裂原活化蛋白激酶（MAPK）和氧化还原敏感性转录因子如核因子-κ B和激活蛋白-1在COPD中发挥增强炎症的作用。此外，MAPK家族的激活导致转录因子和辅激活因子的反式激活（染色质重塑）。这最终导致调节一系列不同的促炎、抗氧化和应激反应基因的基因表达。氧化应激的存在对肺生理学的若干事件和COPD的发病机制具有重要后果。这些包括肺微血管系统中中性粒细胞的隔离增加、抗蛋白酶和表面活性剂的氧化失活、粘液分泌过多、膜脂质过氧化、线粒体呼吸、肺泡上皮损伤/渗透性、细胞外基质的分解/重塑和细胞凋亡。氧化应激可能与皮质类固醇治疗COPD疗效差有关。这篇综述讨论了吸烟和氧化应激在COPD发病机制中的细胞和分子变化。
Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by airflow limitation, which is largely irreversible. Oxidative stress and inflammation are the major hallmarks of COPD. Reactive oxygen species, either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal and F-2-isoprostanes, may play a role in enhancing the inflammation through the activation and phosphorylation of mitogen-activated protein kinases (MAPKs) and redox-sensitive transcription factors such as nuclear factor-kappa B and activator protein-1 in COPD. In addition, activation of the MAPK family leads to the transactivation of transcription factors and coactivators (chromatin remodeling). This eventually results in expression of genes regulating a battery of distinct proinflammatory, antioxidant, and stress response genes. The presence of an oxidative stress has important consequences on several events of lung physiology and for the pathogenesis of COPD. These include increased sequestration of neutrophils in the pulmonary microvasculature, oxidative inactivation of antiproteases and surfactants, hypersecretion of mucus, membrane lipid peroxidation, mitochondrial respiration, alveolar epithelial injury/permeability, breakdown/remodeling of extracellular matrix, and apoptosis. Oxidative stress may have a role in the poor efficacy of corticosteroids in COPD. This review discusses cellular and molecular changes that occur in response to smoking and oxidative stress in the pathogenesis of COPD.