中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1324-1333.doi: 10.4103/1673-5374.327348

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

锂促进脊髓损伤后的恢复

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Lithium promotes recovery after spinal cord injury

Ying-Jie Zhao1, Hao Qiao1, Dong-Fan Liu1, Jie Li1, Jia-Xi Li1, Su-E Chang1, Teng Lu1, Feng-Tao Li1, Dong Wang1, Hao-Peng Li1, Xi-Jing He1, 2, *, Fang Wang1, *   

  1. 1Department of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China; 2Department of Orthopedics, Xi’an International Medical Center Hospital, Xi’an, Shaanxi Province, China
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Xi-Jing He, PhD, MD, xijing_h@vip.tom.com; Fang Wang, MD, wfcn664845753@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81701223 (to FW), 81601081 (to SEC); and the Natural Science Foundation of Shaanxi Province of China, Nos. 2017JQ8019, 2021JM-290 (both to FW). 

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摘要：

锂同时与氧化应激和细胞焦亡存在一定联系，但其对脊髓损伤保护作用的机制仍有待研究。（1）实验发现给脊髓挫伤模型大鼠腹腔注射LiCl治疗后，脊髓的病理损伤有所减轻，肿瘤坏死因子α、白细胞介素6以及白细胞介素1β的表达被抑制，锂通过抑制脊髓损伤后的Caspase-1表达、氧化应激反应以及NLRP3炎症小体的激活，从而抑制了细胞焦亡和炎症反应。（2）通过锂干预氧糖剥夺PC12细胞模型研究锂的神经保护作用机制，发现锂可减轻该细胞模型中的炎症、氧化损伤以及细胞的焦亡和坏死，且上调Nrf2和HO-1的水平；而Nrf2抑制剂全反式维甲酸则可逆转锂的作用。（3）上述结果提示锂可通过Nrf2/HO-1通路发挥抗炎、抗氧化及抗焦亡作用，促进了脊髓损伤的恢复。实验于2018年10月23日经西安交通大学动物伦理委员会批准（批准号2018-2053）。

https://orcid.org/0000-0002-1873-7807 (Ying-Jie Zhao); https://orcid.org/0000-0002-0465-5376 (Xi-Jing He); https://orcid.org/0000-0003-4344-7905 (Fang Wang)

关键词: 锂, 脊髓损伤, 抗焦亡, 抗氧化, 抗炎, 神经保护, 炎症因子, Nrf2, HO-1, 神经元, 细胞死亡

Abstract: Lithium is associated with oxidative stress and apoptosis, but the mechanism by which lithium protects against spinal cord injury remains poorly understood. In this study, we found that intraperitoneal administration of lithium chloride (LiCl) in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factor α, interleukin-6, and interleukin 1 β. Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression, reducing the oxidative stress response, and inhibiting activation of the Nod-like receptor protein 3 inflammasome. We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells. We found that lithium reduced inflammation, oxidative damage, apoptosis, and necrosis and up-regulated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 in PC12 cells. All-trans retinoic acid, an Nrf2 inhibitor, reversed the effects of lithium. These results suggest that lithium exerts anti-inflammatory, anti-oxidant, and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury. This study was approved by the Animal Ethics Committee of Xi’an Jiaotong University (approval No. 2018-2053) on October 23, 2018.

Key words: anti-inflammatory, anti-oxidant, anti-pyroptosis, cell death, inflammatory factors, lithium, neurons, neuroprotective, Nrf2/HO-1, spinal cord injury

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