中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (3): 687-696.doi: 10.4103/1673-5374.380905

• 原著:神经损伤修复保护与再生 • 上一篇    

激活G蛋白偶联受体39可改善神经病理性疼痛

  

  • 出版日期:2024-03-15 发布日期:2023-09-02
  • 基金资助:
    国家自然科学基金项目(82071556和82271291)

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

Longqing Zhang, Xi Tan, Fanhe Song, Danyang Li, Jiayi Wu, Shaojie Gao, Jia Sun, Daiqiang Liu, Yaqun Zhou, Wei Mei*   

  1. Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2024-03-15 Published:2023-09-02
  • Contact: Wei Mei, PhD, wmei@hust.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82071556 and 82271291 (both to WM).

摘要:

有研究表明,激活的G蛋白偶联受体39可通过与SIRT1和过氧化物酶体增殖物激活受体γ共激活因子1α相互作用来减轻炎症反应;但G蛋白偶联受体39是否也参与神经病理性疼痛,目前尚不可知。为此,实验以坐骨神经分支保留性损伤模拟大鼠神经病理性疼痛,可见其脊髓背角中神经元和小胶质细胞中G蛋白偶联受体39表达水平显著下降。鞘内注射G蛋白偶联受体39特异性激动剂TC-G 1008可显著缓解坐骨神经分支保留性损伤大鼠的机械性痛觉异常,改善脊髓线粒体生物发生功能,并减轻神经炎症。且G蛋白偶联受体39 siRNA,SIRT1特异性抑制剂Ex-527以及过氧化物酶体增殖物激活受体γ共激活因子1α siRNA均可抑制TC-G 1008对坐骨神经分支保留性损伤的作用。提示激活G蛋白偶联受体39可通过激活下游sirtuin 1/过氧化物酶体增殖物激活受体γ共激活因子1α信号通路,缓解坐骨神经分支保留性损伤大鼠的机械性痛觉异常。  

https://orcid.org/0000-0001-6556-6628 (Wei Mei)

关键词: GPR39, SIRT1, 神经病理性疼痛, 脊髓, 神经炎症, PGC-1α, NRF1, TFAM

Abstract: Activated G-protein-coupled receptor 39 (GPR39) has been shown to attenuate inflammation by interacting with sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). However, whether GPR39 attenuates neuropathic pain remains unclear. In this study, we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats. Intrathecal injection of TC-G 1008, a specific agonist of GPR39, significantly alleviated mechanical allodynia in the rats with spared nerve injury, improved spinal cord mitochondrial biogenesis, and alleviated neuroinflammation. These changes were abolished by GPR39 small interfering RNA (siRNA), Ex-527 (SIRT1 inhibitor), and PGC-1α siRNA. Taken together, these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1α pathway in rats with spared nerve injury.

Key words: G-protein-coupled receptor 39 (GPR39), neuroinflammation, neuropathic pain, nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), sirtuin 1 (SIRT1), spinal cord, mitochondrial transcription factor A (TFAM)