支气管哮喘气道上皮细胞的线粒体功能研究进展

Advances in mitochondrial function of airway epithelial cells in the bronchial asthma

支气管哮喘(简称哮喘)是一种气道慢性炎症性疾病,其特征包括气道高反应性(airway hyperresponsiveness,AHR)、嗜酸性粒细胞增多、IgE升高、杯状细胞化生和气道重塑等。气道上皮结构与功能的变化是哮喘的突出特征,哮喘气道上皮对氧化剂引起的损伤和细胞凋亡异常敏感,更易受到浸润性炎症细胞产生的活性氧(reactive oxygen species,ROS)的影响,ROS的蓄积和氧化应激是哮喘发病的关键环节。ROS等氧化剂会干扰上皮细胞的结构,致气道重塑;反之,气道重塑会释放炎性介质加重哮喘。线粒体的主要功能是氧化磷酸化合成ATP,也是ROS的重要来源。线粒体功能障碍包括能量代谢转换障碍、线粒体生物学功能障碍、线粒体自噬及动力学异常、线粒体依赖性信号通路障碍。线粒体功能障碍和细胞缺氧在支气管哮喘的发生发展中发挥了极其重要的作用,该文对近年来哮喘气道中气道上皮细胞的线粒体功能改变作一综述,旨在为以线粒体为靶向的哮喘治疗提供理论依据。

Bronchial asthma is a chronic inflammatory disease of the airways,which is characterized by airway hyperresponsiveness(AHR),eosinophilia,elevated IgE,goblet cell metaplasia,airway remodeling and so on.Changes in airway epithelial structure and function are prominent features of asthma.Asthma airway epithelium has abnormal sensitivity to oxidative damage and apoptosis,and is more susceptible to reactive oxygen species(ROS)produced by infiltrating inflammatory cells.The effects of ROS accumulation and oxidative stress are the key links in the pathogenesis of asthma.Oxidants such as ROS can interfere with the structure of epithelial cells and cause tracheal remodeling.Conversely,tracheal remodeling can release inflammatory mediators and aggravate asthma.The main function of mitochondria is oxidative phosphorylation to synthesize ATP,and it is also an important source of ROS.Mitochondrial dysfunction includes energy metabolism conversion dysfunction,mitochondrial biological dysfunction,mitochondrial autophagy and kinetic abnormalities,and mitochondrial-dependent signaling pathway disorders.Mitochondrial dysfunction and cellular hypoxia play an extremely important role in the occurrence and development of bronchial asthma.This article reviews the changes in mitochondrial function of airway epithelial cells in asthma airways in recent years,in order to provide theoretical basis for mitochondria-targeted asthma treatment.