PLTP在慢性阻塞性肺疾病小气道重构中的作用及机制研究

项目名称： PLTP在慢性阻塞性肺疾病小气道重构中的作用及机制研究

项目编号： No.81200009

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 陈亚娟

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 小气道重构（SAR）是导致慢性阻塞性肺疾病（COPD）患者致残率及病死率上升的主要决定性因素，其致病机制错综复杂，目前尚未阐明。虽然国内外新近研究显示肺脏具有强大的脂质代谢能力，本课题组前期研究亦证实磷脂转运蛋白（PLTP）在肺损伤中参与调控TGF-β1表达，但脂负荷对SAR的影响及作用尚未见报道。 本课题拟利用基因敲除鼠复制COPD动物模型，明确PLTP基因缺失对小气道及TGF-β1，Ras/ERK活性的影响；应用RNA干扰诱导PLTP低表达，在体内以期证实PLTP作为Ras/ERK下游信号蛋白参与调控TGF-β1活性表达的具体分子机制。如获成功，不仅有助于进一步揭示SAR具体发病机制，也可为逆转COPD小气道重构提供新的治疗靶点。

中文关键词： 磷脂转运蛋白；烟熏提取物；转化生长因子-beta1；凋亡；上皮间质转化

英文摘要： SAR (Small airway remodeling) is a process in response to long-term, unresolved airway inflammation that results in permanent structural changes in airway wall. Airway structural changes cause irreversible airflow obstruction, which is tightly correlated with the severity of airway inflammatory diseases including COPD (chronic obstructive pulmonary disease) and asthma, and makes treatment of those patients difficult. Smoking is by far, the most common risk factor for COPD. Subepithelial fibrosis is characteristic of airway remodeling and TGF-β (transforming growth factor beta) is the key factor involved in modulating fibrosis. Furthermore, the mechanisms of small airway remodeling are complicated and remain to be determined. As we know, the lung is the most important organ involved in the lipid metabolites. Also, our previous studies have demonstrated that PLTP (phospholipid transfer protein) is an important factor that may play a vital role in the lung injury observed in human alveolar epithelial cells. Thus, modulation of TGF-β by lipid metabolites appears to be a novel strategy for alleviating the small airway remodeling in COPD patients. The aim of this study is to determine whether PLTP can suppress TGF-β production released by cigarette smoke-stimulation in vitro and in vivo and , if so , how it achieves t

英文关键词： phospholipid transfer protein；Cigarette smoke extract；transforming growth factor-β1；apoptosis；epithelial-mesenchymal transition