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产氢硅基制剂改善神经性疼痛大鼠的神经脱髓鞘病变

Amelioration of nerve demyelination by hydrogen-producing silicon-based agent in neuropathic pain rats.

作者信息

Mu Guo, Li Qiang, Lu Bin, Yu Xuan

机构信息

Department of Anesthesiology, Zigong Fourth People's Hospital, Zigong, Sichuan Province 643000, PR China; Laboratory of Anesthesiology, Southwest Medical University, Luzhou, Sichuan Province 646000, PR China.

Department of Anesthesiology, Zigong Fourth People's Hospital, Zigong, Sichuan Province 643000, PR China.

出版信息

Int Immunopharmacol. 2023 Apr;117:110033. doi: 10.1016/j.intimp.2023.110033. Epub 2023 Mar 16.

DOI:10.1016/j.intimp.2023.110033
PMID:36933448
Abstract

Trigeminal neuralgia (TN) is a complex orofacial neuropathic pain. The crippling condition's underlying mechanism is still not completely understood. The main cause of lightning-like pain in patients with TN may be chronic inflammation that causes nerve demyelination. Nano-silicon (Si) can safely and continuously produce hydrogen in the alkaline environment of the intestine to exert systemic anti-inflammatory effects. Hydrogen has a promising anti-neuroinflammatory impact. The study aimed to determine how intra-intestinal application of a hydrogen-producing Si-based agent affected the demyelination of the trigeminal ganglion in TN rats. We discovered that increased expression of the NLRP3 inflammasome and inflammatory cell infiltration occurred concurrently with demyelination of the trigeminal ganglion in TN rats. We could determine that the neural effect of the hydrogen-producing Si-based agent was connected to the inhibition of microglial pyroptosis by using transmission electron microscopy. The results demonstrated that the Si-based agent reduced the infiltration of inflammatory cells and the degree of neural demyelination. In a subsequent study, it was discovered that hydrogen produced by a Si-based agent regulates the pyroptosis of microglia may through the NLRP3-caspase-1-GSDMD pathway, preventing the development of chronic neuroinflammation and consequently lowering the incidence of nerve demyelination. This study offers a novel strategy for elucidating the pathogenesis of TN and developing potential therapeutic drugs.

摘要

三叉神经痛(TN)是一种复杂的口腔面部神经性疼痛。这种致残性疾病的潜在机制仍未完全明确。TN患者闪电样疼痛的主要原因可能是导致神经脱髓鞘的慢性炎症。纳米硅(Si)能在肠道碱性环境中安全持续地产生氢气,从而发挥全身抗炎作用。氢气具有良好的抗神经炎症作用。本研究旨在确定肠道内应用产氢硅基制剂对TN大鼠三叉神经节脱髓鞘的影响。我们发现,TN大鼠三叉神经节脱髓鞘的同时,NLRP3炎性小体表达增加和炎性细胞浸润。通过透射电子显微镜观察,我们可以确定产氢硅基制剂的神经效应与抑制小胶质细胞焦亡有关。结果表明,硅基制剂减少了炎性细胞浸润和神经脱髓鞘程度。在后续研究中发现,硅基制剂产生的氢气可能通过NLRP3 - 半胱天冬酶 - 1 - GSDMD途径调节小胶质细胞焦亡,防止慢性神经炎症的发展,从而降低神经脱髓鞘的发生率。本研究为阐明TN的发病机制及开发潜在治疗药物提供了一种新策略。

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