CFTR负调节的NF-κB/COX-2/PGE2信号通路在烧伤吸入性损伤导致的呼吸道炎症中的作用

项目名称： CFTR负调节的NF-κB/COX-2/PGE2信号通路在烧伤吸入性损伤导致的呼吸道炎症中的作用

项目编号： No.81201464

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 陈婧

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 烧伤吸入性损伤后,肺部炎症有极高的发病率和致死率.其肺部炎症表现为过量炎症介质的释放和相互作用,形成炎症放大级连反应.囊性纤维化病(CF)患者突出表现为过剩的肺部炎症,其病理过程与烧伤吸入性损伤后肺部炎症极其相似,且高温引起细胞膜上有功能的CFTR蛋白表达下调.本项目组前期研究在大鼠原代支持细胞中验证了CFTR表达的温度敏感性以及受CFTR负调节的NF-κB/COX-2/PGE2号通路在CF肺部炎症病理过程中的重要作用.本项目旨在探索CFTR/NF-κB/COX-2/PGE2信号通路在烧伤吸入性损伤引起的呼吸道炎症中的作用,在体外用高温处理正常人类支气管上皮细胞系,体内建立干热和湿热大鼠吸入性损伤模型,分别验证该通路. 本研究可加深对目前烧伤吸入性损伤引起的呼吸道炎症病理生理过程的理解,可能对该病的治疗提供新的靶标和理论依据.

中文关键词： 吸入性损伤；CFTR；MAPK；NF-kB；炎症

英文摘要： The occurrence and mortality of pulmonary inflammation after hyperthermal smoke inhalation are extremely high. The key characteristic of this pathological process is that excessive production of inflmmatory mediators interact with each other to form an inflammatory cascade,which leads to exggerated inflammatory response. Cystic Fibrosis(CF) exhibits overinflammation in the lung, which resembles the pathological condition of hyperthermal smoke inhalation induced pulmonary inflammation. Furthermore, high temperature leads to downregulation of functional CFTR expression on the cell membrane.We have previouly demonstrated the temperature sensitive characteristic of CFTR in primary rat Sertoli cells and a NF-κB/COX-2/PGE2 pathway negatively regulated by CFTR in the pathogenesis of CF airway inflammation. This project aims to investigate the role of CFTR/NF-κB/COX-2/PGE2 pathway in hyperthermal smoke inhalation induced airway inflammation. This study deepens our understanding of the pathological process of hyperthermal smoke inhalation, and may provide new targets for the treatment.

英文关键词： thermal inhalation injury；CFTR；MAPK；NF-kB；inflammation