非经典途径细胞焦亡在脓毒症中的研究进展

Recent advances in non-canonical pyroptosis during sepsis

脓毒症是宿主对感染产生的失控反应,并出现危及生命的器官功能障碍。细胞焦亡(pyroptosis)是一种以促炎性为特点,依赖于Caspase酶活性的细胞程序性死亡。根据发生机制,将细胞焦亡分为经典焦亡途径和非经典焦亡途径。胞内脂多糖通过结合并激活Caspase-11/4/5,进而剪切并激活Gasdermin D蛋白,分离出活性GSDMD-N端,在胞膜形成gasdermin孔道,诱导细胞焦亡,称之为非经典途径细胞焦亡。细胞焦亡是一把双刃剑,一方面可以抵御病原体感染,另一方面能够导致邻近细胞和组织炎症反应,导致机体全身炎症反应。扩展对细胞焦亡分子机制及作用的认识有助于探索脓毒症治疗的新靶点。

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Pyroptosis is a kind of programmed cell death which characterized as proinflammatory and dependents on the caspase enzyme activity.Its development is mediated by canonical or non-canonical pathways according to the molecular mechanism.Caspase-11/4/5 is activated via combining to the intracellular lipopolysaccharide,and thus cleaves gasdermin D,thereby releasing its N domain with the pore-forming activity,which forms a large pore in the membrane that induces non-canonical pyroptosis.Pyroptosis is a double-edged sword,which could contribute to immune defense against pathogen infection on one hand.however,on another hand,it induces inflammation of adjacent cell or organs causing systemic inflammation.Expand our knowledge of pyroptotic molecular mechanism and effect is beneficial to explore new potential targets for sepsis therapy.