氧化应激导致的线粒体功能障碍是驱动COPD病理过程的关键因素。我们前期研究发现孕激素能改善氧化应激诱导的支气管上皮细胞线粒体功能障碍，但分子机制不明确。我们提出P4经PR介导快速诱导c-MYC表达，通过SIRT1/PGC-1α信号轴调控下游基因，从而改善氧化应激导致的线粒体功能障碍，拮抗COPD的炎症反应和气道重构。拟采用CRISPR/Cas9基因敲除术、基因芯片、激光共聚焦等方法研究孕激素处理前后及PR、c-MYC、SIRT1基因敲除前后支气管上皮和气道平滑肌细胞氧化应激导致的线粒体形态、功能变化和炎症反应；并利用COPD氧化应激动物模型和临床病例探讨孕激素对线粒体功能障碍、炎症反应和气道重构的影响。从分子、细胞、动物模型和临床四个层面阐明孕激素拮抗氧化应激诱导的线粒体功能障碍，改善COPD病理过程的作用机制，有望为COPD防治提供新策略。

Oxidative stress–induced mitochondria dysfunction is a pivotal factor of the exacerbation of chronic obstructive pulmonary disease (COPD). Our preliminary study found that progesterone reversed the mitochondrial dysfunction of bronchial epithelial cells via alleviating oxidative stress, but the mechanism is still underdetermined. We propose that progesterone could reverse mitochondrial dysfunction and then antagonize COPD inflammatory response and airway remodeling by inducing instant c-MYC expression through progesterone receptor (PR), regulating downstream genes expression by SIRT1/PGC-1a axis. We will study the morphological and function changes of mitochondria and inflammatory response after treating bronchial epithelial cells and airway smooth muscle cells with progesterone and/or knockdown the genes expression of PR, c-MYC, SIRT1 by CRISPR/Cas9 technique, gene microarray and immunofluorescence staining. Furthermore, in the research level of molecular, cell, animal model and clinical specimen, we will verify whether progesterone could ameliorate exacerbation of COPD by reversing the mitochondria dysfunction and inflammatory response. In our present study, we hope for providing a novel way to prevent the development of COPD.