自噬在器官缺血再灌注损伤中具有重要功能，但在不同器官、不同细胞及不同病理阶段中自噬发挥的调节作用不尽相同。本课题组前期发现自噬在肺缺血再灌注后发生增加并正向调控损伤后无菌性炎症强度，鉴于无菌性炎症和纤维化是肺缺血再灌注损伤后两个关键的病理阶段，进一步研究该疾病模型中自噬的分子调控机制，对于揭示肺缺血再灌注损伤的调控和干预措施具有重要意义。我们通过肺组织的基因芯片筛选出丝/苏氨酸磷酸酶PHLPP1，发现其在肺缺血再灌注后表达显著增加。我们预实验进一步发现PHLPP1可以上调肺缺血再灌注后自噬发生水平，并且促进损伤后肺部无菌性炎症和纤维化，提示PHLPP1通过调控自噬影响肺缺血再灌注损伤。本项目将利用PHLPP1基因敲除小鼠深入研究PHLPP1对自噬或自噬相关基因的作用及在肺缺血再灌注损伤后炎症及纤维化中的调控机制，揭示自噬调控肺缺血再灌注损伤的关键分子环节，为相关疾病临床干预提供理论基础。

Autophagy plays an important role in ischemia-reperfusion (I/R) injury, while has different effects in different organs, cells and pathological process of I/R injury. Our previous study has found that autophagy can function as a positive regulator to enhance aseptic inflammatory responses induced by lung I/R injury. In view of the aseptic inflammation and fibrosis are two key pathological processes in lung I/R injury, the further research of the regulatory mechanism underlying autophagy can help us find the measures to regulate and prevent lung I/R injury. We found that the expression of serine/threonine phosphatase PHLPP1 was significantly increased in lung tissue after lung I/R injury through microarray analysis. However, the function of PHLPP1 in lung I/R injury remains unclear. Our data from the preliminary experiments showed that PHLPP1 could induce autophagy in lung tissue after lung I/R injury, which in turn promoted aseptic inflammation responses and fibrosis in injured lung，suggesting that PHLPP1 could regulate lung I/R injury by autophagy. In this project, we will use PHLPP1 knock-out mice to investigate the interactions between PHLPP1 and autophagy or autophagy-related genes, and further reveal the role of these above interactions in the regulation of inflammation responses and fibrosis after lung I/R injury and the underlying mechanism. The primary aim of this study is to clarify key points in the regulation of lung I/R injury by autophagy, which will may provide new theoretical basis for the clinical intervention and treatment of diseases related to organ I/R injury.