前庭核ALOX12诱导铁死亡参与前庭性偏头痛的作用及机制研究

前庭性偏头痛（VM）是引起反复发作性眩晕的第二大常见原因，被认为是偏头痛的变异体。前庭核作为前庭神经冲动传导的中继站，在VM的发生发展中发挥重要作用，但其作用机制尚未明确。我们前期研究发现，慢性偏头痛模型的前庭核神经元放电模式改变；前庭核中ALOX12介导的脂质过氧化、氧化应激通路激活，铁含量、铁死亡关键分子PTGS2/COX2、NOX1等的表达也显著上调。但脂质过氧化和铁死亡对前庭功能的影响及作用机制尚不明确。我们拟在此基础上，应用两种小鼠偏头痛模型，通过前庭功能评估、电生理记录技术、组织学分析和分子生物学技术研究：1）前庭核的ALOX12介导的脂质过氧化的作用；2）铁死亡对前庭功能的作用及机制；3）ALOX12增高对铁死亡通路的调控机制，并探索ALOX12抑制剂的治疗效果。本项目或为明确VM发病机制提供理论基础，并为探索VM治疗新策略提供思路。

Vestibular migraine (VM) is the second-ranked recurrent vertigo disease，and it is well acknowledged as a variant of migraine. Vestibular nucleus, which acts as a relay station for the conduction of vestibular nerve impulses, plays a critical role in the occurrence and development of VM. However, its mechanism and function remain unclear. Our previous research by the chronic migraine model found that the discharge pattern of vestibular nucleus neurons was altered, the ALOX12 mediated lipid peroxidation pathway and oxidative stress pathway were activated, and the iron level and the key molecules of ferroptosis, PTGS2/COX2, NOX1, etc. were significantly up-regulated. However, the specific role and regulatory mechanism of lipid peroxidation and ferroptosis in VM still need exploring. Based on these observations, we plan to apply two mouse migraine models, and conduct vestibular function assessment, electrophysiological recording, histological analysis and molecular biology techniques to verify: 1) the role of ALOX12-mediated lipid peroxidation in the vestibular nucleus, 2) the effect and mechanism of ferroptosis on vestibular dysfunction, 3) the regulation mechanism of ALOX12 on the ferroptosis pathway, and the therapeutic effects of ALOX12 inhibitors in VM. This project will be beneficial in providing theoretical basis and novel therapeutic strategy in VM.