自噬在脓毒症中的作用及靶向治疗研究进展

The role of autophagy in sepsis and progress in targeted therapy

最新脓毒症定义为宿主对感染的反应失调引起威胁生命的器官功能障碍,具体发病机制尚未完全阐明。自噬作为各类物种间相对保守的调控细胞状态的重要形式,是机体对外界刺激的应答以吞噬外来病原体、损伤的细胞器以及降解失活的蛋白质形式来维持细胞的内部稳态和缓解脓毒症导致的多器官功能障碍(MODS)。免疫细胞功能障碍被认为是脓毒症患者预后不良的主要原因,目前尚缺乏特定的治疗方法。有证据表明利用多种药物激活自噬可以有效缓解脓毒症、改善免疫功能、提高生存率。调控自噬机制可能是逆转脓毒症患者免疫抑制状态的治疗新策略。

Sepsis is currently defined as life-threatening organ dysfunction caused by the host's maladjusted response to infection.The specific pathogenesis has not been fully elucidated.Autophagy,as an important form of relatively conservative regulation of cell state among various species,is the body's response to external stimuli in the form of phagocytosis of foreign pathogens,damaged organelles and degradation of inactivated proteins to maintain the internal homeostasis of cells and relieve multiple organ dysfunction caused by sepsis(MODS).Immune cell dysfunction is considered to be the main cause of poor prognosis in patients with sepsis,and specific treatment is stil lacking.There is evidence that activation of autophagy with multiple drugs can effectively relieve sepsis,improve immune function and improve survival rate.Regulating autophagy mechanism may be a new therapeutic strategy to reverse immunosuppression in sepsis patients.