炎性小体在诱导脊髓损伤神经炎症中的作用

Role of Inflammasomes in Inducing Neuroinflammation in Spinal Cord Injury

脊髓损伤的治疗与康复一直是医学领域的重大难题,尤其是在改善损伤的神经功能方面进展甚微。继发性损伤是造成脊髓损伤后神经功能障碍的主要原因,炎症反应是继发性损伤阶段最重要的病理过程。急性期通过抑制神经炎症来减轻继发性损伤被认为可减轻神经功能损害而达到神经保护作用。炎性小体是一类蛋白质复合体,由模式识别受体中的NLRs家族和PHYIN家族的受体蛋白质作为主要框架组装并命名,常见的炎性小体包括NLRP1、NLRP3、NLRC4(IPAF)、AIM2等。在感染或受到损伤刺激时,炎性小体在细胞质内组装,并激活促炎症蛋白酶胱天蛋白酶1(caspase-1),活化的胱天蛋白酶1一方面促进促炎症细胞因子IL-1β和IL-18的前体成熟和分泌,另一方面介导细胞焦亡。细胞焦亡以细胞肿胀破裂并释放细胞内容物为特征,是在炎症和应激的病理条件下诱导的程序性细胞死亡方式。促炎症细胞因子和焦亡释放的胞内物质都可作为促炎信号引发炎症反应。近期发现,炎性小体通过诱导促炎因子释放以及介导细胞焦亡等途径,参与激活脊髓损伤后的炎症级联反应,加重继发性神经炎症。靶向抑制炎性小体的激活可减轻炎症反应,促进神经细胞存活,达到神经保护作用。因此,炎性小体有望成为脊髓损伤治疗的新靶点。本文拟从炎性小体的结构及其在脊髓损伤中的作用、激活机制和治疗前景进行综述,以期为后续研究提供思路。

Treatment and rehabilitation of spinal cord injury has been a major problem in the medical field,and little progress has been achieved in the improvement of neuronal function following injury.Secondary damage is the main cause of neurological dysfunction after spinal cord injury,and inflammation is the most important pathological process in the secondary injury stage.In the acute phase,it is believed that the reduction of secondary damage by inhibiting neuroinflammation can reduce the damage of nerve function and achieve neuroprotection.The inflammasome is a type of protein complex,which is assembled and named by the receptor proteins of the NLRs family and the PHYIN family of pattern recognition receptors as the main framework.Common inflammasomes include NLRP1,NLRP3,NLRC4(IPAF),and AIM2 etc.When infected or stimulated by injury,inflammasomes assemble in the cytoplasm and activate the pro-inflammatory protease caspase-1.Activated caspase-1 promotes the maturation and secretion of pro-inflammatory cytokines IL-1βand IL-18 on the one hand,and mediates pyroptosis on the other hand.Pyroptosis is a way of programmed cell death induced under pathological conditions of inflammation and stress.Cell swelling and rupture and the release of cell contents are its main characteristics.Both pro-inflammatory cytokines and intracellular substances released by pyroptosis can be used as pro-inflammatory signals to trigger an inflammatory response.Recently,it has been discovered that inflammasomes participate in the activation of the inflammatory cascade after spinal cord injury by inducing the release of pro-inflammatory factors and mediating pyroptosis,and then aggravate secondary neuroinflammation.Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response,promote the survival of nerve cells,and achieve neuroprotective effects.Therefore,the inflammasome is expected to become a new target for the treatment of spinal cord injury.This article reviewed the structure of the inflammasome and its role in spinal cord injury,activation mechanism and treatment,which may provide ideas for the follow-up research.