硫化与大麻素2受体相互作用 在坐骨神经损伤引起的神经病变疼痛期间
Xue Bai1,2, Gerard Batallé1,2, Ignacio Martínez-Martel1,2
1Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain.
Antioxidants (Basel, Switzerland)
|June 28, 2023
概括
硫化 (H2S) 捐赠者增强了大麻素受体2 (CB2R) 激动剂JWH-133的强化作用.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 疼痛研究 疼痛研究
背景情况:
- 神经病痛涉及复杂的炎症和神经营养失调.
- 大麻素受体2 (CB2R) 激动剂显示出缓解疼痛的潜力.
- 硫化 (H2S) 可以调节疼痛通路.
研究的目的:
- 为了调查H2S捐赠者 (DADS,GYY4137) 是否在神经病痛的小鼠模型中增强CB2R激动剂JWH-133的止痛,抗焦虑和抗抑郁作用.
- 探索涉及CB2R,NF-κB,BDNF和Nrf2/HO-1通路的潜在分子机制.
主要方法:
- 利用一个坐骨神经损伤 (CCI) 鼠标模型来诱导神经病痛.
- 系统和局部给药JWH-133,有或没有H2S捐赠者 (DADS,GYY4137).
- 评估了镇痛,缓解焦虑和抗抑郁行为;在大脑区域 (PFC,vHIP,PAG) 分析了分子标志物 (p-IKBα,BDNF,CB2R,Nrf2,HO-1) 并使用了CB2R抗剂 (AM630).
主要成果:
- H2S捐赠者显著改善了JWH-133的止痛作用.
- 同时使用GYY4137和JWH-133可减少神经病痛相关的焦虑和抑郁.
- H2S捐赠者使炎症和神经变标记正常,增加CB2R表达,并激活Nrf2/HO-1抗氧化途径.
- 通过AM630阻断止痛,表明内分泌系统参与H2S效应.
结论:
- 在神经病痛中,H2S供体增强了CB2R激动剂在神经病痛中的治疗效果.
- 组合疗法解决了疼痛和相关的情绪障碍.
- 这种协同作用突显了神经病痛和相关并发症的有前途的治疗策略.
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