SARS-CoV、H5N1型高致病性禽流感、2009甲型H1N1、人H7N9禽流感等往往导致急性肺损伤（Acute Lung Injury，ALI），并进一步发展为急性呼吸窘迫综合征，由于防治手段有限，病死率高达30%-70%。ALI最重要的病理生理改变是肺气血屏障损伤，因此深入研究肺气血屏障损伤的分子机理有着重要意义。本项目拟针对多种病原体导致的ALI，在病人水平、动物水平和细胞水平上，结合全蛋白组修饰测序等高通量研究方法，研究病原体通过何种方式导致细胞因子/趋化因子炎症信号网络异常、抑制AMP－CFTR；并进一步研究病原体如何导致宿主的稳态维持系统发生紊乱和自噬性细胞死亡通路激活，从而解析肺气血屏障发生发展过程中的关键机制；最后，可通过肺功能检测平台和多项生理病理指标评估针对新靶点药物的防治疗效。本课题的实施将为研发新型的ALI干预药物提供科学依据。

Diverse pathogens, such as SARS Coronavirus, highly pathogenic H5N1 avian influenza virus, H1N1 influenza A virus in 2009 and H7N9 avian influenza virus, can induce acute lung injury (ALI), then further develop into acute respiratory distress syndrome (ARDS). With limitation of current prophylactic and therapeutic measures, the morality of ALI/ARDS is as high as 30-70%. The most important pathological and physiological change induced by ALI/ARDS is the damage of lung blood-air barrier, thus, focusing on molecular mechanisms of this damage may significantly speed up the researches and developments on drugs to treat ALI. In order to understand the critical pathogenic mechanisms during development of damage of lung blood-air barrier, this project will focus on ALI induced by different types of pathogens at the level of patients, animal and cell models.Through protein modification sequencing and other methods, we will systematically discuss the patterns and mechanisms of pathogens’ immune escape, theuncontrollable inflammatory responses by studying inflammatory signaling networks of cytokines/chemokines and inhibition of inflammatory regulator cAMP-CFTR.Furthermore, we will deeply investigate the mechanisms of how pathogens induce the disorder of homeostasis-maintenance system, such as Angiotensin II‘s overexpression in RAS system during pathogens’ infection. After all, the pulmonary function-detecting platform and multi-physiological and pathological.indexes will be used to evaluate the potential candidate drugs’ prophylactic andtherapeutic effects. Briefly, this project will provide solid scientific bases fordeveloping novel drugs to treat ALI.