高压氧通过抑制NLRP3炎症小体活化改善颅脑神经组织损伤的研究  

Improving effect of hyperbaric oxygen on craniocerebral nerve injury through inhibiting NLRP3 inflammasome activation

作　　者：温亚[1] 白思怡 李燕[1] Wen Ya;Bai Siyi;Li Yan(Department of Emergency,Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Guangxi Medical University,Nanning 530100,China)

机构地区：[1]山西医科大学第二医院急诊科,太原030001 [2]广西医科大学,南宁530100

出　　处：《中华航海医学与高气压医学杂志》2023年第5期555-559,共5页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

基　　金：山西省重点研发计划项目(201903D321017)。

摘　　要：目的探讨高压氧通过阻碍NOD样受体热蛋白结构域相关蛋白-3(NLRP3)炎症小体活化抑制颅脑神经组织损伤的机制。方法选取60只成年健康雄性SD大鼠,按随机数字表法分为假手术组、颅脑损伤组、高压氧组,每组20只。采用限制性皮层损伤法对颅脑损伤组和高压氧组大鼠进行损伤手术建模,建模6 h后,高压氧组予以高压氧治疗,连续治疗7 d。分别于颅脑损伤模型完成后第1、3、7天采用改良神经功能缺损评分(mNSS)评估各组大鼠的神经功能,采用酶联免疫吸附实验检测大鼠脑组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-18的表达水平,Western blotting实验检测大鼠脑损伤区脑组织中NRLP3、胱天蛋白酶-1(caspase-1)的相对表达量。TUNEL法检测各组大鼠的神经元凋亡率。结果与假手术组比较,脑损伤组和高压氧组大鼠各时间点mNSS评分明显升高(P<0.01);高压氧组大鼠第3天和第7天mNSS评分明显低于同期脑损伤组(P<0.05)。与假手术组比较,脑损伤组和高压氧组大鼠第7天脑组织中IL-1β、TNF-α、IL-18水平明显升高(P<0.01);高压氧组大鼠第7天脑组织中IL-1β、TNF-α、IL-18明显低于同期脑损伤组(P<0.05)。与假手术组比较,脑损伤组和高压氧组大鼠第7天脑组织中NLRP3、caspase-1相对表达量明显升高(P<0.01);高压氧组大鼠第7天脑组织中NLRP3、caspase-1相对表达量明显低于同期脑损伤组(P<0.05)。与假手术组比较,脑损伤组和高压氧组大鼠第7天脑组织中神经元凋亡率明显升高(P<0.01);高压氧组大鼠第7天脑组织中神经元凋亡率明显低于同期脑损伤组(P<0.05)。结论高压氧可通过抑制NLRP3炎症小体活化缓解机体炎症反应,减少神经元凋亡,有效缓解神经功能缺损,进一步改善颅脑损伤,具有较好治疗效果。Objective To investigate the mechanism of hyperbaric oxygen inhibiting further craniocerebral nerve tissue injury through blocking the activation of NOD-like receptor pyrin domain-related protein 3(NLRP3)inflammasome.Methods A total of 60 healthy adult male SD rats were selected and divided into sham operation group,traumatic brain injury(TBI)group,and hyperbaric oxygen(HBO)group according to the random number table method,with 20 rats in each group.Surgical induction of restricted cortical injury was performed on the rats of the TBI group and the HBO group.On 6 h after modeling,the HBO group was treated with HBO therapy for seven days.On the 1st,3rd,and 7th day after the completion of TBI modeling,the neural function of each group was evaluated by modified neurological severity score(mNSS),and the expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-18 in the brain tissue were detected by enzyme-linked immunosorbent assay.Moreover,Western blotting was conducted to detect relative expressions of NRLP3 and caspase-1 in the brain tissue at the brain injury area,and TUNEL assay was used to test the apoptosis rate of neurons in each group.Results Compared with the sham operation group,mNSS scores in the TBI group and the HBO group significantly increased at each time point(P<0.01),and the mNSS scores in the HBO group on day 3 and day 7 were significantly lower than those in the TBI group(P<0.05).Compared with the sham operation group,the levels of IL-1β,TNF-α,and IL-18 in the brain tissue of the rats in the TBI group and the HBO group significantly increased on day 7(P<0.01);on day 7,the levels of IL-1β,TNF-α,and IL-18 in the brain tissue of the rats in the HBO group were significantly lower than those in the TBI group(P<0.05).Compared with the sham operation group,the relative expressions of NLRP3 and caspase-1 in the brain tissue of the rats in the TBI group and the HBO group significantly increased on day 7(P<0.01);on day 7,the relative expressions of NLRP3 and caspase-1 in the

关 键 词：颅脑损伤 高压氧 NOD样受体热蛋白结构域相关蛋白⁃3 炎症小体 

分 类 号：R651.1[医药卫生—外科学]