目前对慢阻肺仍然缺乏生物标志物和针对呼吸道病理改变有效的治疗措施。炎症反应、氧化应激、及其引发的肺内实质细胞凋亡促进慢阻肺。GLIPRl调控肿瘤细胞凋亡，但其在COPD病变进展中的作用未明。我们前期研究发现，慢阻肺患者血浆中GLIPR1 mRNA阳性的外泌体丰度显著高于健康吸烟人群；GLIPR1主要表达于肺部上皮细胞，烟熏诱导其选择性及代偿性上调；敲减GLIPRl抑制uPA/uPAR和KRT15，引起线粒体介导的细胞凋亡。因此，我们推测GLIPR1在慢阻肺发生发展中具有重要作用。本研究拟利用基于脂质体复合物纳米颗粒生物芯片研究外泌体内GLIPR1 mRNA与慢阻肺急性发作、预后和分级的相关性；通过Glipr1基因敲除小鼠，探讨Glipr1对气道炎症和肺内上皮细胞凋亡的影响及机制；利用Krt15-LacZ基因报告小鼠，研究Krt15在慢阻肺发生发展中的作用，为慢阻肺的防治提供新的思路。

Currently, there is still a lack of biomarkers and efficient treatments for Chronic Obstructive Pulmonary Disease (COPD). Airway inflammation, oxidative stress, and the apoptosis of epithelial and endothelial cells play important roles in COPD. GLI pathogenesis-related 1 (GLIPR1) regulates the apoptosis of cancer cells; however, the role of GLIPR1 in COPD is not clear. In previous studies, we found that the level of GLIPR1 mRNA in plasma exosomes from patients with COPD was significantly higher than that from healthy smokers. GLIPR1 was mainly expressed in the airway epithelial cells, and cigarette smoke compensatorily upregulated the expression of GLIPR1. GLIPR1 knockdown significantly increased the apoptosis of epithelial cells, possibly through the urokinase plasminogen activator system (uPA/uAPR) and/or Keratin 15 (KRT15). Therefore, we hypothesize that GLIPR1 plays an important role in COPD. Using the tethered cationic lipoplex nanoparticle (TCLN) technique, we propose to study the association between the level of GLIPR1 mRNA in the circulating exosomes and the development of COPD and the severity and frequency of COPD exacerbations. Using the Glipr1 knockout mice, we propose to evaluate the role of Glipr1 in airway inflammation and the apoptosis of epithelial cells. Using the Krt15-LacZ reporter mice, we propose to study the role of Krt15 in the development of COPD. Our studies will provide potential pharmacological targets for the treatment of COPD.