不同脏腑虚损慢阻肺患者气道上皮CFTR功能差异及肺离子细胞对慢阻肺小鼠气道黏液屏障的调控作用研究

慢阻肺的发病与肺、脾、肾三脏虚损密切相关，可造成不同程度的卫气功能下降和痰饮内生，而外邪入里与痰饮互结可导致慢阻肺反复急性加重的发生。气道黏液屏障作为人体固有免疫的一部分，是抵御致病原侵入呼吸系统的第一道防线，其功能紊乱可造成慢阻肺的发生、发展。本研究通过对不同脏腑虚损慢阻肺患者的鼻粘膜电位差及采用靶向测序技术对CFTR、FOXI1基因进行测定，从蛋白质功能和基因差异方面发现导致慢阻肺患者气道黏液屏障功能下降的关键因素，探究其在不同脏腑虚损状态下的变化规律。同时采用PH荧光探针、激光共聚焦显微镜等技术评价慢阻肺小鼠气道上皮表面黏液的变化状况；以流式细胞及scRNA-seq技术发现气道上皮中肺离子细胞（一种新发现的细胞）数量、凋亡情况及表达CFTR关键通路的变化特点，从而揭示肺离子细胞在慢阻肺发病过程中的作用，从新的视角探讨导致慢阻肺反复发作的生物学内涵，同时为慢阻肺的防治提供新的研究思路。

The progression of COPD is closely related to the viscera deficiency of lung, spleen and kidney. It can cause the decline of defence function and endogenous phlegm in different degrees.The combination of exogenous pathogens and phlegm can lead to the occurrence of repeated acute exacerbation of COPD. Airway mucus barrier, as a part of human innate immunity, is the first line of defense against pathogens invading the respiratory system. Its dysfunction can cause the occurrence and development of COPD. In this study, by detecting the NPD and the CFTR,FOXI1 genes with targeting sequencing technique, the key factors leading to the decline of airway mucus barrier function in COPD patients were found from the aspects of protein function and gene difference,and the changing rules of COPD patients with different viscera deficiency were explored. PH fluorescence probe and laser confocal microscopy were used to evaluate the changes of ASL on airway epithelium of COPD mice. Flow cytometry and scRNA-seq were used to detect the characteristics of the number, apoptosis and the key pathway of CFTR expression of pulmonary ionic cells (a newly discovered cell) in airway epithelium in COPD mice, so as to reveal the role of pulmonary ionocytes in the pathogenesis of COPD. To explore the biological connotation of recurrent COPD from a new perspective, and to provide new research ideas for the prevention and treatment of COPD.