病毒感染是COPD急性发作最早最常见触发诱因，肺泡巨噬细胞识别感染危险信号后，快速启动一系列炎症反应致COPD急性发作，但发生机制不明。预实验结果证实：流感病毒检测阳性AECOPD患者，其血清和BALF中载脂蛋白ApoE水平显著降低,IFN-γ,TNF-α,IL-6,CCL-2等含量显著升高。因此，我们提出假设：ApoE通过与气道上皮细胞高亲和性低密度脂蛋白受体LDLR结合，在调控流感病毒诱发AECOPD气道炎症风暴中扮演重要角色。本实验采用：①流感病毒H3N2诱发ApoE和LDLR基因敲除的COPD小鼠模型；②原代气道上皮细胞CRISPR/Cas9敲除和慢病毒过表达LDLR，然后分别检测ApoE/LDLR表达和细胞/炎症因子含量的改变，以探讨ApoE/LDLR信号通路在气道炎症风暴发生中分子机制，为临床寻找阻断病毒诱导AECOPD的药物新靶点提供理论依据。

Viral infection is the earliest and most common trigger for acute exacerbation of COPD. After the alveolar macrophage recognizes the danger signal of infection, it quickly triggers a series of inflammatory reactions to cause acute exacerbation of COPD, however the mechanism is unknown. Pre-experimental results confirmed that in AECOPD patients with influenza virus positive, the levels of apolipoprotein E in serum and BALF were significantly reduced and the levels of IFN-γ, TNF-α, IL-6 and CCL-2 were significantly increased. Therefore, we hypothesized that ApoE plays an important role in the regulation of influenza virus-induced AECOPD airway inflammation storms by binding to high-affinity low-density lipoprotein receptor (LDLR) in airway epithelial cells. This experiment used: 1. Infecting COPD mouse models induced with ApoE or LDLR gene knockout with influenza virus H3N2. 2. On the basis of primary airway epithelial cells with CRISPR/Cas9 knockout or LDLR overexpressed transfected by lentivirus, detecting the expression of ApoE/LDLR and the levels of cytokines or inflammatory factors respectively. We aim to explore the molecular mechanism of ApoE/LDLR signaling pathway in the occurrence of airway inflammation storm in order to provide theoretical basis for the clinical search of new targets for blocking virus-induced AECOPD.