阻断NLRP3介导的细胞焦亡对创伤性脑损伤小鼠的保护作用

Protective effects of inhibiting NLRP3 mediated pyroptosis on traumatic brain injury mice

目的探讨抑制NLRP3炎症小体、减少细胞焦亡对创伤性脑损伤(TBI)小鼠的保护作用。方法将36只BALB/c小鼠随机均分为假损伤组、TBI模型组、MCC950(CP-456773)治疗组。采用自由落体法构建小鼠TBI模型,造模后按时腹腔注射MCC950或生理盐水适量。通过HE染色、尼氏染色评价各组小鼠脑组织损伤情况,免疫荧光法检测其脑组织中NLRP3、Caspase1及GSDMD的表达。结果HE染色显示,与假损伤组比较,TBI组小鼠脑损伤区域神经元数量减少,神经元胞核固缩、深染,胞核周围出现大量空泡;MCC950治疗组神经元状态明显优于TBI组。尼氏染色,MCC950治疗组脑组织神经元缺失及损伤情况较TBI组均明显改善。免疫荧光显示,与TBI组比较,MCC950治疗组的脑组织冰冻切片NLRP3、Caspase1及GSDMD表达量均较TBI组明显降低。结论MCC950可能通过抑制NLRP3炎性小体介导的细胞焦亡,减轻TBI小鼠脑组织的创伤及细胞结构损伤。

Objective To investigate the protective effects of MCC950 on traumatic brain injury(TBI)mice by inhibiting pyroptosis via suppressing NLRP3 inflammasome.Methods A total of 36 BALB/c mice were randomly divided into the following groups:a sham injury group,a TBI model group,a MCC9501-day and 7-day treatment group.The TBI model of mice was induced by free fall method,and MCC950 was intraperitoneally injected into the treatment group after modeling.HE staining and nissl staining were used to evaluate the brain tissue injury conditions of each group.The expressions of NLRP3,Caspase1 and GSDMD in each group were detected by the immunofluorescence.Results H&E staining showed that compared with the sham injury group,the number of neurons in the injured area in the TBI model group decreased,and the nuclei of neurons were consolidated and hyperchromatic,with a large number of vacuoles around the nuclei.The neuron status of the TBI+MCC950 treatment group(1-day and 7-day treatment group)were significantly better than that of the TBI model group.Nissl staining showed that compared with the TBI model group,the neuron loss and injury in the TBI+MCC950 treatment group(1-day and 7-day treatment group)attenuated.Immunofluorescence showed that compared with the TBI model group,the expression levels of NLRP3,caspase1 and GSDMD in frozen sections of brain tissues of the TBI+MCC950 group(1-day and 7-day treatment group)significantly reduced.Conclusions Application of MCC950 in the treatment of TBI mice can effectively inhibit NLRP3-mediated pyroptosis and alleviate the damage of brain tissue and cell structure at the wound site.