香烟诱导的气道炎症与黏液高分泌是慢阻肺重要的病理生理学特征，其具体机制尚未明确。我们前期研究发现靶基因与线粒体调控相关的miR-200家族参与了香烟诱导气道上皮炎症损伤与黏液高分泌,其机制可能与调控线粒体损伤相关分子模式（MTDs）释放，介导TLR-9与FPR信号通路有关。为验证上述学术假说，本研究将通过临床研究、基因敲除/转基因、RNA干扰、特异性抑制剂/激动剂等研究手段，探明：1）吸烟对miR-200家族、MTDs及其相关信号通路的影响，明确其慢阻肺标记物功能；2）不同类型MTDs诱导气道上皮炎症损伤的机制与特点，miR-200家族调控MTDs释放参与香烟诱导炎症与黏液高分泌的具体分子机制；3）开展基于miR-200家族及MTDs相关信号通路（TLR-9/FPR-1/FPR-2）干预性研究，为香烟诱导的气道炎症与黏液高分泌寻找到新的干预靶点。

Cigarette smoke-induced airway inflammation and mucus hypersecretion is one the most important features of COPD, while its mechanism remains unclear. Our previous study found that miR-200 family, which target genes related with mitochondrion, is involved in cigarette smoke -induced airway inflammation and mucus hypersecretion, and miR-200 family may play a role in the regulation of MTDs release, which mediated subsequent airway epithelium inflammatory injury and mucus hypersecretion through TLR-9 and FPR signal pathways. To validate the above academic hypothesis, in this study, we will perform studies involving clinical research, gene knockout and transgene, RNA interference, specific inhibitor/ agonist to explore: 1) the effects on cigarette smoke exposure on miR-200, MTDS and MTDs related signal pathways, and investigate the possibility of miR-200 and MTDs as biomarker of COPD; 2) the characteristics of different MTDs induced airway inflammatory response, and the molecular mechanism of miR-200 family mediated MTDs release and its role in cigarette smoke-induced airway inflammation and mucus hypersecretion; 3) the effects of interventions based on miR-200 family, MTDs related signal pathway (TLR-9/FPR-1/FPR-2) on cigarette smoke-induced airway inflammation and mucus hypersecretion, and try to find a novel therapeutic target for cigarette smoke induced inflammation and mucus hypersecretion.