自噬清除活化的炎性体抑制DAMPs诱导的肺损伤的实验研究

项目名称： 自噬清除活化的炎性体抑制DAMPs诱导的肺损伤的实验研究

项目编号： No.81460292

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘芬

作者单位： 南昌大学

项目金额： 49万元

中文摘要： 最新研究提示细菌感染并不是导致SIRS 的唯一致病因素，文献报道和我们的前期研究发现，线粒体来源的DAMPs（MTDs ）是内源性DAMPs的主要来源之一，其可通过多种途径引起炎症细胞炎性体活化和炎症因子失控性释放，是严重创伤、休克时肺损伤发生的主要机制。然而，能否通过清除活化的炎性体，阻断MTDs致炎作用尚待研究。近来研究发现炎性体的活化可诱导细胞内自噬，而自噬反馈性清除活化的炎性体并抑制其诱导的炎症反应。因此，本项目拟采用MTDs 诱导肺泡巨噬细胞炎症反应，观察调控肺泡巨噬细胞自噬水平后，自噬对活化的炎性体的清除作用及对炎症因子的影响，探讨其抑制MTDs诱导炎症反应的作用及机制；然后通过雾化吸入雷帕霉素或重组慢病毒载体pLenex-Beclin1，靶向上调大鼠肺内的自噬水平，探讨其对MTDs 诱导的肺损伤的保护作用，为严重创伤、休克导致的肺损伤提供新的治疗途径。

中文关键词： 肺损伤；损伤相关分子模式；炎性体；自噬

英文摘要： A growing body of evidence suggests that bacterial infections are not the only causative factor of systemic inflammatory response syndrome (SIRS). are components from. Our recent studies and those from others have shown that Majority of endogenous DAMPs are components from mitochondria-derived DAMPs (MTDs), it trigger inflammasome activation and abnormal release of inflammatory cytokines, which is the underlying mechanism in trauma- and shock-induced lung injury. However how to block MTDs-triggered inflammatory by diminishing the activated inflammasome has been further study. Several lines of new evidence suggest that inflammasome activation can induce cellular autophagy. Autophagy could negatively feedback to diminish inflammasome resulting in ameliorating inflammatory. In the current proposal, to elucidate mechanisms by which autophagy inhibits DAMPs-induced inflammatory, we will modulate autophagy level to investigate how it culls inflammasome and how it dampens inflammatory cytokines using a MTDs-induced alveolar macrophage inflammatory model. To further explore protective effect of autophagy on MTDs-induced rat lung injury, rapamycin and pLenex-Beclin1 will be administered through inhalation to finely tune upregulate autophagy level, which may provide a novel therapeutic approach to ameliorate trauma- and shock-induced lung injury.

英文关键词： lung injury;damage-associated molecular patterns (DAMPs);inflamasome;autophagy