中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (8): 1802-1811.doi: 10.4103/1673-5374.389302

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

羽扇烯酮抑制炎症小体改善脊髓损伤引起的运动功能障碍

  

  • 出版日期:2024-08-15 发布日期:2024-01-03
  • 基金资助:
    国家自然科学基金项目(81801226,82101445)

Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

Fudong Li1, 2, #, Xiaofei Sun2, #, Kaiqiang Sun3, #, Fanqi Kong2, *, Xin Jiang4, *, Qingjie Kong1, *   

  1. 1Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Orthopedic Surgery, Spine Center, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China; 3Department of Orthopedic Surgery, Naval Medical Center, Naval Medical University, Shanghai, China; 4Department of Anesthesiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China
  • Online:2024-08-15 Published:2024-01-03
  • Contact: Qingjie Kong, MD, 15900558565@163.com; Xin Jiang, MD, drxjiang@126.com; Fanqi Kong, MD, fanqi_kong@sina.com.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81801226 (to QK and XS) and 82101445 (to XJ).

摘要:

脊髓损伤诱导的运动功能障碍与神经炎症有关。有研究发现,羽扇烯酮是一种广泛存在于多种植物的三萜类化合物,且在慢性炎症环境中存在显著的抗炎活性,但其是否也能对在脊髓损伤诱导的急性炎症产生作用尚未见报道。实验以重物打击法构建了小鼠脊髓损伤模型,而后腹腔注射羽扇烯酮(8 mg/kg,2次/d);并以脂多糖和ATP干预BV2细胞模拟脊髓损伤后的炎症反应。结果显示,羽扇烯酮可减轻IκBα和p65核转位,还可通过调节核因子κB抑制NLRP3炎症小体的产生,也能增强促炎性M1小胶质细胞向抗炎性M2小胶质细胞的转化。此外,羽扇烯酮可通过抑制核因子κB通路改善NLRP3炎症小体的过度激活和NLRP3诱导的小胶质细胞极化和焦亡。由此提出羽扇烯酮可通过抑制炎症小体对脊髓损伤发挥治疗作用。

https://orcid.org/0000-0002-3407-0715 (Fudong Li); https://orcid.org/0000-0002-3788-305X (Qingjie Kong)

关键词: 脊髓损伤, 炎症, 炎症小体, 小胶质细胞, 极化, 焦亡, 羽扇烯酮

Abstract: Spinal cord injury-induced motor dysfunction is associated with neuroinflammation. Studies have shown that the triterpenoid lupenone, a natural product found in various plants, has a remarkable anti-inflammatory effect in the context of chronic inflammation. However, the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown. In this study, we established an impact-induced mouse model of spinal cord injury, and then treated the injured mice with lupenone (8 mg/kg, twice a day) by intraperitoneal injection. We also treated BV2 cells with lipopolysaccharide and adenosine 5′-triphosphate to simulate the inflammatory response after spinal cord injury. Our results showed that lupenone reduced IκBα activation and p65 nuclear translocation, inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B, and enhanced the conversion of proinflammatory M1 microglial cells into anti-inflammatory M2 microglial cells. Furthermore, lupenone decreased NLRP3 inflammasome activation, NLRP3-induced microglial cell polarization, and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway. These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

Key words: inflammasome, inflammation, lupenone, microglia, polarization, pyroptosis, spinal cord injury