偏头痛引起的耳损伤通过CGRP信号传递触发ZBP1介导的PANoptosis
Wandi Xu1, Ni Zhai2,3, Jingyu Chen1
1Department of Otorhinolaryngology, Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
The journal of headache and pain
|February 3, 2026
概括
偏头痛可以通过通过色素基因相关 (CGRP) 损害内耳毛细胞引起听力损失. 阻止CGRP保护听力,为偏头痛相关的听力损伤提供了一个新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
- 药理学 药理学是指药理学的学科.
背景情况:
- 与偏头痛相关的听力异常不太了解,特别是外围影响.
- 素基因相关 (CGRP) 涉及偏头痛病理生理学,但其在内耳损伤中的作用尚不清楚.
研究的目的:
- 为了调查偏头痛如何诱导外周听力损伤.
- 确定在偏头痛期间CGRP在内耳中的作用.
- 探索针对CGRP的潜在听力保护疗法.
主要方法:
- 建立了一个慢性偏头痛 (CM) 鼠标模型,使用酸甘.
- 评估了CGRP信号传递,听觉功能 (ABR,DPOAE) 和外部毛细胞 (OHC) 完整性.
- 研究了CGRP诱导的细胞通路 (线粒体应激,PANoptosis) 在体外和体内.
主要成果:
- CM小鼠表现出听力缺陷和OHC损伤,这些损伤通过Rimegepant (CGRP阻断) 得到改善.
- 在OHC中,CGRP过度刺激导致线粒体应激,mtDNA泄漏和ZBP1介导的PANoptosis.
- 抑制ZBP1和PANoptosis可以减少OHC损伤和听力损失.
结论:
- 外皮毛细胞是CGRP介导的偏头痛引起的听力损失的关键目标.
- CGRP引发细胞内压力和炎症,导致OHC死亡和听力损失.
- 这些发现支持偏头痛引起的听力损失亚型和潜在的听力保护策略.
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