交替氧化酶旁路在气道上皮损伤中的作用研究

Arway inflammation induced by airway epithelial cell injury can lead to a variety of lung diseases, including COPD. At present,there is no specific treatment.In the pre-experiment, the function of cytochrome c oxidase and the ciliary beat frequency are decreased when the airway epithelial cells were damaged by cigarette smoke extract.This phenomenon indicated that mitochondrial electron transport chain was impaired and airway clearance was weakened.Alternative oxidase provide a bypass for the impaired respiratory chain.In this study, we propose that the expression of AOX can repair the damage of airway epithelial cells. Object of study is trying to explore the therapeutic effect of AOX on respiratory diseases with airway inflammation.After successful expression of AOX in airway epithelial cells, it can inhibit the production of reactive oxygen species,increase the degree of ATP andairway cilia beat frequency. It can reduce depolarization of membrane potential, airway hyperresponsiveness and the expression of inflammatory factors in lung tissue.The implementation of this project is expected to open up a new way for airway inflammation treatment.

气道上皮细胞损伤导致的气道炎症可以诱发包括COPD在内的多种肺部疾病，目前对此缺乏特异性的治疗措施。申请人预实验发现吸烟刺激引起气道上皮细胞受损时，细胞色素c氧化酶功能下降且气道纤毛摆动频率降低，提示线粒体电子传递链受损及气道清除作用减弱。交替氧化酶可为受损的呼吸链建立一个旁路作用，本项目提出将AOX在哺乳动物气道上皮细胞内表达来修复气道上皮细胞损伤，研究AOX在以气道炎症为基础病变的呼吸系统疾病中的治疗作用，具体论证下述推断：在气道上皮细胞表达AOX，可抑制香烟刺激造成的细胞活性氧产生，减轻 ATP降低程度，减弱膜电位去极化，恢复气道纤毛摆动频率，减缓气道高反应性，使肺组织炎症因子表达减少。本项目的实施有望为气道上皮细胞受损造成的气道炎症治疗开辟一条新的探索途径。