中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 350-356.doi: 10.4103/1673-5374.346457

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

敲除沉默信息调节因子2基因可减轻创伤性脑损伤

  

  • 出版日期:2023-02-15 发布日期:2022-08-08
  • 基金资助:
    中国国家自然科学基金项目(81671207,81974189)

Knockout of Sirt2 alleviates traumatic brain injury in mice

Wei Wang, Qiu-Yuan Gong, Lin Cai, Yao Jing, Dian-Xu Yang, Fang Yuan, Hao Chen, Heng-Li Tian*   

  1. Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
  • Online:2023-02-15 Published:2022-08-08
  • Contact: Heng-Li Tian, MD, PhD, tianhlsh@126.com.
  • Supported by:
    This work was supported by the National Nature Science Foundation of China, Nos. 81671207 and 81974189 (both to HLT).

摘要:

有研究显示抑制或敲除沉默信息调节因子2可对神经退行性疾病和脑缺血具有保护作用,但其是否也对创伤性脑损伤也有作用,目前仍然不明。因此实验建立了敲除沉默信息调节因子2小鼠创伤性脑损伤模型。结果发现,敲除沉默信息调节因子2可减轻创伤性脑损伤小鼠的脑水肿以及血脑屏障的破坏,减少核苷酸结合寡聚化结构域样受体蛋白3炎性小体和细胞焦亡水平,并显著改善其神经功能。在进一步体内实验中,敲除机械拉伸损伤模拟创伤性脑损伤细胞模型中的沉默信息调节因子2,也证实其降低核苷酸结合寡聚化结构域样受体蛋白3炎症小体的表达及效应子caspase-1的活性,并减轻神经炎症和细胞凋亡。上述结果提示,敲除沉默信息调节因子2基因可对创伤性脑损伤产生脑保护作用,因而可能成为治疗创伤性脑损伤的新靶点。

https://orcid.org/0000-0003-0525-503X (Heng-Li Tian)

关键词: 创伤性脑损伤, 沉默信息调节因子2, 血脑屏障, 脑水肿, 紧密连接蛋白, 核苷酸结合寡聚化结构域样受体蛋白3, caspase-1, 神经炎症, 细胞焦亡, 神经保护

Abstract: Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment. 

Key words: blood-brain barrier, caspase-1, cerebral edema, neuroinflammation, neuroprotection, NLRP3, pyroptosis, Sirt2, tight junction protein, traumatic brain injury