目前对慢阻肺仍然缺乏针对呼吸道病理改变有效的治疗措施。有效降低气道炎症及维持上皮细胞屏障稳定性对于防治慢阻肺至关重要。甘油激酶参与游离脂肪酸代谢，在慢性炎症和代谢疾病中具有重要作用，但其在慢阻肺病变进展中的作用未明。我们前期研究发现，甘油激酶5（GK5）在气道上皮细胞表达；动物及细胞实验表明，吸烟代偿性上调GK5及水甘油通道AQP3和AQP9表达；GK5基因敲除显著降低上皮细胞内GAPDH、AQP3和AQP9表达，并伴随细胞迁移能力下降。因此，我们推测GK5在气道炎症及上皮损伤修复中具有重要作用。本项目拟采用吸烟大鼠慢阻肺及烟熏细胞损伤模型，明确GK5对气道炎症和上皮损伤修复的影响；GK5对气道上皮水和甘油通道蛋白表达的影响，水甘油通道AQP9对气道上皮损伤修复的影响及机制，为慢阻肺的治疗提供新的思路。

Currently, there is still a lack of efficient treatments for Chronic Obstructive Pulmonary Disease (COPD). Reducing airway inflammation and.maintaining epithelial barrier function are critical in the prevention and treatment of COPD. Glycerol kinase deficiency-induced elevation of free fat acid plays important roles in chronic inflammation and metabolic disorders. Our previous studies found that,glycerol kinase 5 (GK5) is highly expressed on airway epithelial cells; cigarette smoke extract compensatorily upregulated the expression of GK5 and aquaglyceroporin 3 (AQP3) and AQP9 48hours after epithelial cell injury; GK5 siRNA significantly decreased the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), AQP3, and AQP9 on airway epithelial cells, and reduced epithelial cell migration. Therefore, we hypothesize that GK5 plays an important role in reducing airway inflammation and maintaining airway epithelial barrier function. We propose to study the effects of GK5 on the airway inflammation and the repair of epithelial cells after injury using both in vivo and in vitro models; the effects and mechanism of GK5 knockdown and overexpression on the gene and protein expression of aquaporins and aquaglyceroporins; the effects and mechanism of AQP9 on wound healing of airway epithelial cells. Our studies will provide potential pharmacological targets for the treatment of COPD.