中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 456-462.doi: 10.4103/1673-5374.346547

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鞘内注射利普司他汀1抑制铁死亡并减轻炎性疼痛

  

  • 出版日期:2023-02-15 发布日期:2022-08-09
  • 基金资助:
    广东省基础与应用基础研究基金项目

Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund’s adjuvant-induced inflammatory pain

Yi-Fan Deng1, Ping Xiang2, Jing-Yi Du1, Jian-Fen Liang1, Xiang Li1, *   

  1. 1Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 2Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • Online:2023-02-15 Published:2022-08-09
  • Contact: Xiang Li, PhD, lixiang27@mail.sysu.edu.cn.
  • Supported by:
    This work was supported by the Basic and Applied Basic Research Foundation of Guangdong Province, No. 2021A1515220081 (to XL).

摘要:

以往研究已经确定了铁依赖性铁死亡与周围神经损伤引起的神经性疼痛之间的关系;然而,铁死亡在炎性疼痛中的作用还没有定论。在此,实验拟探讨脊髓和背根神经节中的铁死亡是否与完全弗氏佐剂诱导的大鼠疼痛行为有关。结果显示,在完全弗氏佐剂诱发的炎性疼痛大鼠模型脊髓和DRG组织中出现了多种与铁死亡有关的生化和形态学变化,如铁超载、脂质过氧化增强、长链脂酰辅酶 A 合成酶4(ACSL4)和谷胱甘肽过氧化物酶4(GPX4)水平紊乱,以及线粒体的形态学异常变化。鞘内注射铁死亡抑制剂利普司他汀1可以逆转这些与铁死亡相关的异常改变,并减轻完全弗氏佐剂诱发的炎性疼痛。这些结果表明鞘内注射利普司他汀1是治疗炎性疼痛的一种潜在治疗策略。

https://orcid.org/0000-0003-4997-9339 (Xiang Li)

Abstract: Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model. However, the role of ferroptosis in inflammatory pain remains inconclusive. Therefore, we aimed to explore whether ferroptosis in the spinal cord and dorsal root ganglion contributes to complete Freund’s adjuvant (CFA)-induced painful behaviors in rats. Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats. These changes included iron overload, enhanced lipid peroxidation, disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels, and abnormal morphological changes in mitochondria. Intrathecal treatment of liproxstatin-1 (a ferroptosis inhibitor) reversed these ferroptosis-related changes and alleviated mechanical and thermal hypersensitivities in CFA rats. Our study demonstrated the occurrence of ferroptosis in the spinal cord and dorsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of ferroptosis inhibitors, such as liproxstatin-1, is a potential therapeutic strategy for treating inflammatory pain.

Key words: cell death, complete Freund’s adjuvant, dorsal root ganglion, ferroptosis, inflammatory pain, intrathecal delivery liproxstatin-1, spinal cord