炎症反应是急性肺损伤重要病理变化，而肺微血管内皮屏障功能在炎症反应的渗出环节起关键作用。本课题组前期发现，Apelin-13可以减轻LPS诱导的急性肺损伤和内皮细胞VE-cadherin的破坏，但增加了自噬水平。因此我们推测，Apelin-13的保护作用可能通过激活线粒体自噬和增加线粒体合成保护线粒体功能，减轻内皮屏障的破坏。为此，我们拟在前期工作基础上，采用基因敲除鼠，结合抑制剂、RNA 干扰、细胞分子生物学技术，旨在动物模型及细胞水平上阐明Apelin-13在急性肺损伤中保护肺血管内皮细胞屏障功能的具体机制；探讨Apelin-13维持线粒体功能与调控线粒体合成和自噬的关系。从而在体内和体外验证假说：Apelin-13对急性肺损伤的防治作用与其调控线粒体合成和自噬，稳定线粒体功能，保护肺血管内皮屏障相关，从而为急性肺损伤疾病的治疗和新药开发提供全新的理论依据。

Acute lung injury is acute and progressive respiratory failure induced by multiple pathogenic factors. The inflammatory response is an important pathological change of acute lung injury, and the pulmonary microvascular endothelial barrier plays a key role in the diapedesis. Our previous results indicate that Apelin-13 reduces the mitochondrial damage, the destruction of VE-cadherin between pulmonary artery endothelial cells and increases the level of autophagy to protect the acute lung injury induced by LPS in mice.Herein, we hypothesize that the protective effect of Apelin-13 may protect mitochondrial function by activating mitophagy and increasing mitochondrial biosynthesis to reduce ROS production which can destroy the endothelial barrier. According to the previous results, our project plans to construct acute lung injury models, use PGC-1α，PINK knock-out mice and pulmonary artery endothelial cells, inhibitors, RNA interfere and cell molecular biology techniques to clarify the role of Apelin-13 in protecting pulmonary microvascular endothelial barrier in acute lung injury in vivo and vitro, confirm that this protection is relation to mitochondrial biosynthesis and mitophagy, supply new theory evidences for the clinical treatment and new drug development of acute lung injury.