Wang Wei, Gong Qiu-Yuan, Cai Lin, Jing Yao, Yang Dian-Xu, Yuan Fang, Chen Hao, Tian Heng-Li
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Neural Regen Res. 2023 Feb;18(2):350-356. doi: 10.4103/1673-5374.346457.
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.
在动物模型中，抑制沉默调节蛋白2（SIRT2）或敲除Sirt2基因可预防神经退行性疾病和脑缺血的发生。然而，SIRT2在创伤性脑损伤（TBI）中的作用仍不清楚。在本研究中，我们发现，在TBI小鼠模型中敲除Sirt2基因可减轻脑水肿，减轻血脑屏障破坏，降低核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体的表达，降低效应半胱天冬酶-1的活性，减轻神经炎症和神经元焦亡，并改善神经功能。在体外机械拉伸损伤细胞模型中敲除Sirt2基因也可降低NLRP3炎性小体的表达和焦亡。我们的研究结果表明，敲除Sirt2基因对TBI具有神经保护作用；因此，Sirt2可能是TBI治疗的新靶点。
