中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (9): 4311-4321.doi: 10.4103/NRR.NRR-D-25-00990

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

司美格鲁肽在创伤性脑损伤抗炎及机神经保护的双重作用

  

  • 出版日期:2026-09-15 发布日期:2026-05-21
  • 基金资助:
    北京市科技计划项目（Z201100005520039）和首都医科大学自然科学基金（PYZ23123）

Semaglutide alleviates neuroinflammation and exerts neuroprotective effects by blocking IL-17/NLRP 3-mediated positive feedback between peripheral and innate immunocytes following traumatic brain injury

Bin Zhang1, #, Lu Kong2, #, Yumei Wang1, #, Wei He3, #, Mengshi Yang1, Xueling Zhang1, Xiyu Chen1, Yaxuan Zhang1, Baiyun Liu4, Miao Bai5, *, Guangzhi Shi1, *   

  1. 1Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 
    2Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, Shandong Province, China; 
    3Department of Neurosurgery, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong Province, China; 
    4Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 
    5Department of Neurology, The First Hospital of Tsinghua University, Beijing, China
  • Online:2026-09-15 Published:2026-05-21
  • Contact: Miao Bai, MD, bmsmile7906@163.com; Guangzhi Shi, MD, shiguangzhi@bjtth.org.
  • Supported by:
    This study was supported by Beijing Science and Technology Plan Project, No. Z201100005520039 (to GS); the Natural Science Foundation of Capital Medical University, No. PYZ23123 (to BZ).

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摘要：

长效胰高血糖素样肽-1受体激动剂司美格鲁肽对脑卒中及神经退行性疾病具有显著神经保护作用，但其在创伤性脑损伤后的抗炎及屏障保护效应及其机制尚不明确。实验采用小鼠建立可控皮质撞击损伤模型，深入探究司美格鲁肽对创伤性脑损伤后神经炎症、血脑屏障完整性与通透性、脑水肿及神经功能恢复的影响机制。研究结果表明，塞玛格鲁肽治疗可减轻白细胞介素-17/NOD样受体嘌呤结构域含蛋白3诱导的神经炎症，上调紧密连接蛋白表达水平，从而减少脑组织渗漏与脑水肿，促进神经功能恢复。透射电镜评估进一步证实，司美格鲁肽能维持血脑屏障超微结构完整性，增强内皮细胞膜间的紧密连接。其作用机制在于通过阻断由白细胞介素-17/NOD样受体嘌呤结构域含蛋白3诱导的外周及先天免疫细胞炎症正反馈循环来缓解炎症状态。综上，研究揭示了司美格鲁肽在抗炎与神经保护中的双重作用，为其在创伤性脑损伤急性期的临床转化应用提供了重要前临床证据。


https//orcid.org/0009-0002-0480-5474 (Miao Bai); 

https//orcid.org/0000-0003-4189-5800 (Guangzhi Shi)

关键词: 凋亡, 血脑屏障, 脑水肿, 胰高血糖素样肽-1受体, 白细胞介素17, 神经炎症, 神经元存活, 创伤性脑损伤, 继发性脑损伤, 司美格鲁肽

Abstract: Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, exhibits significant neuroprotective effects in stroke and neurodegenerative diseases. However, the anti-inflammatory and barrier-protective effects of semaglutide and the mechanisms underlying its effects following traumatic brain injury remain unclear. In this study, we used mice to establish a model of controlled cortical impact injury to investigate the roles and effects of semaglutide on neuroinflammation, the integrity and permeability of the blood– brain barrier, brain edema, and the recovery of neurological function after traumatic brain injury. Our results showed that semaglutide treatment alleviated interleukin-17/NOD-like receptor pyrin domain-containing 3-induced neuroinflammation and upregulated the expression of tight junction proteins, thereby reducing brain leakage and edema while promoting the recovery of neurological function. Furthermore, transmission electron microscopy assessments demonstrated that semaglutide maintained the ultrastructure of the blood–brain barrier, strengthening the tight junctions between endothelial cell membranes. Mechanistically, semaglutide alleviated inflammatory conditions by interrupting the positive-feedback loop of inflammation in peripheral and innate immune cells induced by interleukin-17/NOD-like receptor pyrin domain-containing 3. Collectively, our findings reveal the dual anti-inflammatory and neuroprotective roles of semaglutide, providing important preclinical evidence for its clinical application in the acute phase of traumatic brain injury. 

Key words: apoptosis, blood–brain barrier, brain edema, glucagon-like peptide-1 receptor, interleukin-17, neuroinflammation, neuronal survival, secondary brain injury, semaglutide, traumatic brain injury