脓毒症患者中高发的脑功能障碍对患者预后有重要影响：其不仅显著增高患者近期死亡率，还通过迁延为慢性认知功能障碍，严重影响存活患者的远期生活质量。目前对此尚无有效治疗措施。我们在前期研究中发现：小鼠在脓毒症后出现持续性认知功能障碍的同时，其大脑海马区也出现了炎症反应关键因子HMGB-1的持续活化以及自噬功能的持续下降。而文献报道，HMGB-1的受体同自噬调控密切相关。据此，我们推测：脓毒症后HMGB-1活化可诱发持续性的中枢神经系统炎症反应和自噬水平下降，最终导致认知功能障碍的发生。为证实这一假说，我们拟利用动物行为学分析和分子生物学技术，通过体内实验和体外实验，探讨抑制HMGB-1和调控自噬对脓毒症后认知功能的影响，并深入探讨HMGB-1通过抑制自噬影响认知功能的分子机理和信号通路。本课题将从全新的角度探讨脓毒症后脑功能障碍的发生机制，为防治脓毒症后认知障碍提供新的药物靶点。

Brain dysfunction is not umcommon in sepsisn patients, which is associated with increased short-term mortality and long-term cognitive decline. Due to a lack of comprehensive understanding of the underlying pathogenesis, there is no effective treatment and preventive measures. In our pilot, we found that, synchronized with the persistent cognitive dysfunction in septic mice, there was a sustained activation of HMGB-1 in the hippocampus of the brain and sustained decline in autophagy. Therefore, we hypothesize that neuroinflammation in CNS secondary to sepsis could impair the function of neuron via modulation of autophagy, eventually leading to the occurrence of cognitive dysfunction. To confirm this, we plan to use animal behavior tests in animals and molecular biology techniques in cultured neurons to evaluate how persistent CNS inflammation and autophagy affect of cognitive function after sepsis, as well as the underlying signaling pathways . This study is designed to explore the pathogenesis of sepsis-induced congnitive disorder from a novel perspective, which would highlight the new potential therapeutic target.