近年来研究表明,线粒体自噬参与脓毒症相关疾病的发生，在脓毒血症所致器官损害，线粒体自噬水平受到明显抑制，通过诱导自噬能够缓解脓毒症所致相关器官的损害。FUNDC1是与线粒体自噬相关的线粒体外膜蛋白，其相关功能的缺失会直接导致线粒体的降解受到一定程度的抑制，从而打破了线粒体的动态平衡。我们前期的工作表明在SAE大鼠模型中FUNDC1表达下降，线粒体自噬受到明显抑制，出现受损线粒体清除障碍。本项目拟以LPS处理SD大鼠皮层原代神经元细胞模型和SAE大鼠模型为研究对象，采用过表达和抑制线粒体自噬调节基因FUNDC1，PINK1-Parkin和Bnip3，探讨线粒体自噬在上述模型中的动态变化及调控和保护机制，阐明FUNDC1介导的线粒体自噬及其他相关基因介导的信号通路在脓毒血症脑病发病机制中的作用，为通过对线粒体自噬途径的调节治疗脓毒血症相关性脑病提供理论依据和靶点。

Recent studies demonstrate that mitochondrial damage is closely linked to inflammatory injuries and to cell death during the septic condition. The activation of mitophagy was inhibited leading to the clearance disorder of damaged mitochondria. FUNDC1 is an outer mitochondrial membrane protein. Defects in function of FUNDC1 have been associated with dysfunction of elimination of damaged mitochondria, which broke the dynamic balance of mitochondria. Our previous work has shown the regulation of mitochondrial autophagy and the degradation of damaged mitochondria is disordered in sepisis associated encephalopathy (SAE) models. In this project, the molecular mechanism of mitochondrial autophagy in SAE is going to study by inducing or inhibiting autophagic adapter gene expression in LPS-induced primary cortical cell and SAE rat model, and discussing the mitophagy dynamics and its significance. Furthermore, this project can also clarify the role of FUNDC1 and other associated genes mediated autophagy and its signaling pathways in the protection of SAE, and provide new targets for the prevention and treatment of SAE through the regulation of mitophagy process.