慢性阻塞性肺疾病（COPD）患者基数庞大，但临床尚无有效防治手段，基础研究缺乏合适动物模型。最新临床研究发现COPD患者弹性蛋白抗体升高，提示其作为自体抗原介导COPD自免疫反应。据此，我们拟参照经典哮喘动物模型，利用弹性蛋白构建COPD急性炎症和慢性肺气肿模型。我们的预实验结果表明，弹性蛋白致敏和短期激发能诱导小鼠气道中性粒细胞炎症、粘液高分泌及Th1/Th17型免疫反应，长期激发则诱导肺气肿，非常吻合COPD的部分临床特征。本项目将进一步完善弹性蛋白诱导的COPD急慢性模型，并深入研究该模型中的自免疫反应机制。主要目标是期望能以COPD自免疫反应为理论基础，成功构建一种简便稳定省时的新型小鼠模型，该模型预期能模拟COPD最主要的临床特征，如中性粒细胞炎症、粘液高分泌、Th1/Th17型免疫反应、肺气肿以及肺功能下降等。本项目有望为COPD研究提供全新方法，并完善COPD免疫学发病机制。

Chronic obstructive pulmonary disease (COPD) is affecting a huge population worldwide, there are however very limited approaches for COPD therapy. The basic research for COPD is at relative low levels, mainly because of lack of appropriate research animal models. Recently it has been observed that anti-elastin antibody was increased in COPD patients, and the elastin peptide could induce a Th1 response in monocytes isolated from peripheral blood of COPD patients, suggesting that elastin may serve as a self-antigen which mediates the COPD autoimmune response. Thus, referring to the typical asthma model, we will try to use elastin to induce a COPD-like airway inflammation and an emphysema phenotype. Our preliminary data showed that sensitization and short-term challenge with elastin induced neutrophilic airway inflammation, mucus hyperproduction, and Th1/Th17 immune responses, while long-term challenge induced emphysema-like phenotype in mouse lung, mimicking the characters of human COPD. We will therefore further improve the models of elastin-induced COPD airway inflammation and emphysema, and will further investigate the molecule mechanisms of the smoking-induced and elastin-mediated COPD autoimmune response. This study, based on the COPD autoimmune response, aims to establish a simple, stable, rapid, and novel COPD mouse model, which can represent most of the human COPD characters including neutrophilic airway inflammation, mucus hyperproduction, Th1/Th17 immune responses, emphysema phenotype, and lung function decline. This project will provide a novel animal model for COPD study, and will add new information to the immune pathogenesis of COPD.