首都医科大学学报 ›› 2025, Vol. 46 ›› Issue (3): 538-544.doi: 10.3969/j.issn.1006-7795.2025.03.019

• 基础研究 • 上一篇    下一篇

益生菌对大鼠热性惊厥发作及海马组织中NOD样受体热蛋白结构域相关蛋白3炎症小体活化的影响

何南1*,王亚龙2   

  1. 1.首都医科大学附属北京潞河医院儿科,北京 101199; 2.北京市通州区妇幼保健院儿科,北京 101101
  • 收稿日期:2024-03-04 出版日期:2025-06-21 发布日期:2025-06-25
  • 通讯作者: 何南 E-mail:henanluhe@163.com

Inhibitory effect of probiotics on febrile seizures in rats through inhibiting NOD-like receptor pyrin domain-containing protein 3 inflammasome in hippocampus

He Nan1*, Wang Yalong2   

  1. 1.Department of Pediatricsei, Beijing Luhe Hospital, Capital Medical University, Beijing 101199, China; 2.Department of Pediatricsei, Beijing Tongzhou Maternity and Child Health Care Hospital, Beijing 101101, China
  • Received:2024-03-04 Online:2025-06-21 Published:2025-06-25

摘要: 目的  探究益生菌对大鼠热性惊厥(febrile seizure,FS)发作及海马组织中NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor pyrin domain-containing protein 3, NLRP3)炎症小体活化的影响。方法  将120只大鼠按随机数法分为空白组、模型组和益生菌治疗组3组,每组各40只。模型组与益生菌组构建 FS 大鼠模型,益生菌组灌胃给予微生态制剂,模型组及空白组给予同样溶剂蒸馏水喂养。干预后对模型组和益生菌组再次热水浴刺激诱发二次 FS 发作,记录相关指标并采集样本进行检测分析。结果  空白组海马区神经细胞结构完整、形态规则、大小均匀;模型组海马带宽窄不一、神经细胞数目减少、排列不规则;益生菌治疗组海马区神经细胞数目较模型组多,细胞结构改变较模型组少。益生菌治疗组FS发作潜伏时间较模型组明显延长,持续时间较模型组明显缩短、发作等级较模型组明显降低(P<0.05)。益生菌治疗组海马组织和血清中NLRP3、白细胞介素-1β、白细胞介素-18蛋白相对表达水平较模型组明显降低,但较空白组明显升高,组间差异均有统计学意义(P<0.05);空白组、益生菌治疗组、模型组双歧杆菌、乳酸杆菌数量依次明显降低,大肠杆菌、粪肠球菌数量依次明显升高,组间差异均有统计学意义(P<0.05);益生菌治疗组血清中二胺氧化酶、D-乳酸、NO浓度较模型组降低,但较空白组升高,组间差异均有统计学意义(P<0.05)。结论  益生菌可有效改善FS发作,可能与其能够抑制NLRP3炎症小体活化、降低炎症因子水平、调节肠道有益菌含量以及维护肠黏膜屏障功能有关。

关键词: 益生菌, 热性惊厥, 大鼠, 海马组织, 3NOD样受体热蛋白结构域相关蛋白3, 炎症小体

Abstract: Objective  To investigate the effect of probiotics on febrile seizures (FS) in rats and NOD-like receptor pyrin domain-containing protein 3(NLRP3) inflammasome activation in hippocampus. Methods  A total of 120 rats were randomly divided into three groups: a control group, a model group, and a probiotic treatment group, with 40 rats in each group. FS rat models were established in both the model group and the probiotic group. The probiotic group was administered with microecological preparations via gavage, while the model group and the control group were fed with distilled water. After the intervention, the model group and the probiotic group were subjected to a hot water bath stimulus again to induce a secondary FS episode. Relevant indicators were recorded, and samples were collected for detection and analysis. Results  For the blank group, the structure of neurons in hippocampus was complete, the morphology was regular, and the size is uniform. For the model group, hippocampal zones varied in width, cell number in hippocampus decreased, and the arrangement of hippocampal neurons was irregular. For the probiotics group, cell number in hippocampus were more than the model group, and the changes in the structure were fewer than those in the model group. Compared with the model group, the latent time of FS was significantly longer, the duration of FS was significantly shorter, and the level of FS was significantly lower in the probiotics group (P<0.05). The relative expression levels of NLRP3, interleukin-1β(IL-1β), and interleukin-18 (IL-18) proteins in hippocampal tissues and serum of the probiotic group were significantly fewer than those in the model group but significantly higher than those in the control group, with statistically significant differences between groups (P<0.05). The numbers of Bifidobacterium and Lactobacillus decreased sequentially from the control group to the probiotic group and then to the model group, while the numbers of Escherichia coli and Enterococcus faecalis increased correspondingly, with statistically significant differences between groups (P<0.05). The levels of dia mine oxidase (DAO), D-lactate, and NO in serum of the probiotic group were lower than those in the model group but higher than those in the control group, with statistically significant differences between groups (P<0.05). Conclusion  Probioticseffectively alleviate FS episodes by inhibiting NLRP3 inflammasome activation, reducing inflammatory cytokine levels, modulating intestinal microbiota composition, and preserving intestinal barrier function, providing a novel strategy for the prevention and treatment of FS.

Key words: probiotics, fever seizures, rat, hippocampus, NOD-like receptor pyrin domain-containing protein 3, inflammasome

中图分类号: