病毒感染是COPD急性加重最常见诱因，而气道上皮细胞炎症小体NLRP3可快速识别病毒感染“危险”信号，从而触发系列炎症反应致COPD急性加重，但其发生机制不甚明了。本项目组研究证实：流感病毒是AECOPD最常见感染病毒，其患者肺泡灌洗液中NLRP3/caspase-1水平显著增高；流感病毒和COPD患者原代气道上皮细胞共培养24h，NLRP3和caspase-1表达显著上调，下游细胞因子IL-1β 和IL-18含量升高。采用慢病毒转染或siRNANLRP3干涉抑制气道上皮细胞改变NLRP3表达量，则其IL-1β 和IL-18表达量呈相应的正、负调控。因此，我们提出假设：病毒激发NLRP3/caspase-1信号通道在AECOPD炎症反应中扮演重要角色。本项目旨在研究流感病毒感染与炎症小体NLRP3在气道炎症信号转导中作用及分子机制，为临床寻找阻断病毒诱导AECOPD药物新靶点提供理论依据。

Respiratory viral infection is recognized as an important trigger for acute exacerbations of COPD. After rapid recognization of viral infection as a dangerous message, NLRP3 inflammasome in epithelial cell cytoplasm is activated and triggers downstream inflammatory response inducing a large number of synthesis and release of inflammatory mediators which ultimately resulted in exacerbations of COPD. However, its possible mechanism remains unclear. Our previous research has confirmed that influenza virus was the most frequently isolated virus in AECOPD, and the expression of NLRP3 and caspase-1increased significantly in BAL in those patients with AECOPD. Furthermore, after co-culture of influenza virus and primary cultured human bronchial epithelial cells from patients of COPD for 24 hours, there was significantly elevated expression of NLRP3 and caspase-1 as well as its downstream cytokins IL-1β and IL-18. After the interference of siRNANLRP3 or transfection of lentivirus changing the expression of NLRP3 inflammasome in bronchial epithelial cells, the secretion of IL-1β and IL-18 were obviously regulated. Therefore, we make a hypothesis that viruses activated NLRP3/caspase-1 signaling pathway plays an important role in inflammatory response in patients of AECOPD. Based on the culture of primary airway epithelial cells, we want to explore the mechanism of influenza virus inducing inflammatory response of AECOPD at molecular biological level, which may provide evidence for exploring therapeutic targets in patients with COPD.