含基蛋白4蛋白通过激活TLR4/NF-kappaB依赖的神经炎症来促进慢性术后疼痛
Ruichen Shu1, Yuan Li1, Zengli Zhang1
1Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
BMC anesthesiology
|July 12, 2025
概括
含有原体的蛋白4 (Brd4) 通过启动脊髓神经炎症来驱动慢性术后疼痛. 用JQ1抑制Brd4有效地阻止疼痛的发展,为持久性疼痛提供了潜在的新疗法.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 疼痛研究 疼痛研究
背景情况:
- 慢性疼痛,特别是术后疼痛,是一种普遍存在且未得到充分治疗的疾病.
- 人们越来越认识到表观遗传修饰是慢性疼痛发展的关键因素.
- 含有odomain的蛋白4 (Brd4) 是理解疼痛慢性化的潜在目标.
研究的目的:
- 研究表观遗传调节器Brd4在慢性术后疼痛的发展中的作用.
- 探索涉及Brd4在疼痛慢性化中的潜在分子机制.
- 在临床前疼痛模型中评估 Brd4 抑制剂的治疗潜力.
主要方法:
- 通过使用皮肤/肌肉切口和收缩,建立了一种慢性术后疼痛的老鼠模型.
- 脊髓组织分析了Brd4表达,TLR4/NF-κB通路激活和细胞因子/化学因子释放.
- 用BET抑制剂JQ1来评估其对疼痛行为和分子标记物的影响.
主要成果:
- 在慢性术后疼痛模型中,脊柱Brd4表达显著上调.
- 观察到TLR4/NF-κB通路的激活和促进炎症媒介的释放增加.
- 取决于剂量,JQ1治疗减少了疼痛行为,并抑制了TLR4/NF-κB激活和相关的炎症媒介.
结论:
- Brd4通过TLR4/NF-κB通路在脊髓中表观遗传调节神经炎症,导致慢性术后疼痛.
- 由JQ1抑制Brd4有效地防止过渡到慢性疼痛.
- 针对Brd4是一个有前途的治疗策略,用于管理持续的术后疼痛.
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