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通过HMGB1-TLR4依赖的微质炎症调解PAG神经NMDARs激活的吗啡诱导的过敏症

Jingjing Mo¹, Zijing Lu², Jialing Peng³

¹Department of Neurology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.

Journal of psychiatric research

|June 23, 2023

概括

长期使用吗啡会通过在周水管灰细胞中的Toll-like受体4 (TLR4) 激活引起阿片类药物诱导的过敏症 (OIH). 这一途径涉及高流动性组盒1 (HMGB1) 和微质,导致神经元过激动性和OIH.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

阿片类药物诱导的过敏症 (OIH) 是一个重要的临床挑战,限制了吗啡的止痛效果.
导致OIH的精确机制,特别是Toll-like受体4 (TLR4) 和谷氨酸受体在周水道灰色 (PAG) 中的作用,仍然不完全理解.

研究的目的:

阐明在OIH期间PAG中TLR4和N-甲基-D-酸盐受体 (NMDARs) 激活之间的关联.
研究微质和特定分子通路在吗啡诱导的过敏症中的作用.

主要方法:

利用OIH的小鼠模型,观察微质激活,TLR4/p65NF-κB信号传递,以及PAG中的NMDAR亚单元酸化.
采用细胞培养 (BV2,N2A) 来研究高流动性组框1 (HMGB1) 的TLR4激活及其对NMDARs的下游影响.
使用TLR4抑制,淘汰和淘汰 (Lentivirus-GFP-TLR4shRNA) 进行干预,以评估它们对OIH的影响.

主要成果:

吗啡诱导微质激活,增加TLR4/p65NF-κB,以及PAG和BV2细胞中的炎症性细胞因子.
吗啡通过HMGB1,而不是MD2激活了TLR4,导致微质衍生炎症,在相邻神经元中化NMDAR子单元 (NR1,NR2B).
在PAG中TLR4淘汰赛逆转了这些分子变化,并显著缓解了OIH症状.

结论:

吗啡诱导的OIH涉及PAG微质中的TLR4激活,由HMGB1.1调解.
激活的微质细胞释放炎症因子,在神经元中酸化NMDARs,增加刺激性并导致OIH.
在PAG中准TLR4/NMDAR通路为管理OIH提供了一个有希望的治疗策略.

关键词:

微质细胞是如何形成的没有NMDAR,没有NMDAR.在OIH中,OIH是OIH.这是PAG的PAG.在 TLR4 中,

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