七氟烷诱导的术后认知功能障碍(POCD)是术后常见并发症，其病理机制尚不完全清楚。申请人前期研究发现，POCD发生伴随大鼠海马神经元自噬障碍，雷帕霉素诱导自噬可减轻七氟烷所致POCD。申请人的预实验有趣地发现，七氟烷导致细胞线粒体自噬障碍，并初步发现线粒体自噬障碍可能参与了其诱导的细胞损伤。七氟烷导致神经元GABA受体重组装，该过程有大量GABARAP参与，申请人提出，七氟烷作用后较长时间内GABARAP与线粒体外膜蛋白BNIP3或BNIP3L结合减少，最终造成线粒体自噬障碍。申请人的预实验也发现GABARAP在七氟烷处理后表达下调。因此，本项目拟进一步利用细胞及动物实验，结合多种分子生物学手段，进一步明确线粒体自噬障碍在七氟烷所致POCD中的作用，并试图阐明GABARAP-BNIP3/BNIP3L通路在上述过程中的参与机制。本研究将有望为发现POCD干预靶点提供实验依据。

Sevoflurane-induced postoperative cognitive dysfunction (POCD) is well-documented in clinic practice. However its underlying mechanisms are poorly understood. Our previous works found sevoflurane-induced POCD was accompanied with autophagy impairment in rat hippocampal neurons. Rapamycin, an autophagy inducer, was found alleviated sevoflurane-induced neuronal injury in rats. Nevertheless, over-activated autophagy is deleterious to neuronal survival. Therefore, it is quite necessary to further identify the detailed mechanisms of sevoflurane-induced POCD and thus to develop the associated drug targets. Our preliminary data interestingly found that sevoflurane led to mitochondria autophagy (mitophagy) impairment, which is involved in sevoflurane-induced cell death. Sevoflurane causes the reassembling of GABA receptors which GABARAP are substantially recruited. GABARAPs are required in mitophagy process by binding with mitochondrial out membrane proteins BNIP3 or BNIP3L. We therefore hypothesized that the uncoupling of GABARAPs and BNIP3/BNIP3L is involved in sevoflurane-induced mitophagy impairment. In this study, we aimed to identify the contributions of impaired mitophagy in sevoflurane-induced POCD and further explore the involvement of GABARAP-BNIP3/BNIP3L pathway in this scenario. The current study will provide critical experimental evidences for the development of therapeutic targets against POCD.