眩晕一直是渡海作战和临床面临的难题之一，目前尚缺乏有效的防治措施。前庭器官毛细胞机械-电转换功能的敏感性改变和异常是产生眩晕的外周关键机制。申请者前期的工作和文献显示，前庭器官毛细胞表达功能性的TRPA1通道，TRPA1通道参与皮肤及内耳机械-电转换，提示开展TRPA1通道在前庭毛细胞机械-电转换中的作用及其机制研究具有关键性作用。根据预实验结果，本项目拟通过基因敲除、RNAi干扰、电生理及行为学等研究，验证TRPA1通道功能影响毛细胞机械-电转换的敏感性进而影响眩晕的发生假设，阐明miR-6715-3p 和 miR-6715-5p调控TRPA1通道影响眩晕发生的关键机制；筛选调控miR-6715-3p 和 miR-6715-5p预防眩晕的药物，揭示TRPA1通道在眩晕中的关键作用及其机制，为研发预防和治疗眩晕的新途径奠定基础。

Vertigo has been the perplexities of medical treatments and sea fights as well. However, little progress has been made in the prevention and treatment of vertigo. The alteration in the sensitivity of mechanical-electronic transfer in vestibular hair cells might be the key peripheral mechanisms underlying vertigo under physiological and pathological conditions. Our preliminary data indicated that the TRPA1 expressed in vestibular hair cells. Taken together with the previous work demonstrating that TRPA1 was involved in mechanical-electronic transfer in inner ear and skin as well, it suggests that the investigation of the role of TRPA1 of vestibular hair cells in mechanical-electronic transfer might find a solution to vertigo. On the basis of our preliminary data showing that the vestibular hair cells expressed TRPA1 and miR-6715-3p and miR-6715-5p etc., this project will perform integrative neurobiological experiments including the gene knockout, RNAi interference, electrophysiological and behavioral assay, to test the hypothesis that TRPA1 is involved in vertigo by affecting the sensitivity of the mechanical-electronic transfer in vestibular hair cells, so as to elucidate the mechanisms underlying the involvement of miR-6715-3p and miR-6715-5p in vertigo by the modulation of TRPA1. Based on these investigations, the project will further screen the candidate medicines targeting at miR-6715-3p and miR-6715-5p for the prevention of treatment of vertigo. The aim of this project is to find out the key roles of TRPA1 in vertigo so as to lay the foundation for the development of novel way to prevent and treat vertigo.

眩晕一直是临床面临的难题之一，目前尚缺乏有效的防治措施。本课题组前期研究发现，前庭器官microRNA可能是在眩晕过程中发挥了重要作用。本研究首先通过旋转刺激构建生理性眩晕小鼠模型。进而运用microRNA芯片，对眩晕过程中的前庭microRNA表达谱进行了系统分析，通过生物信息学靶基因预测和pathway分析，揭示了神经生长因子（NGF signaling）和轴突导向因子（Axon guidance）等信号通路参与调控眩晕过程。研究结果为研发预防和治疗眩晕提供了有用的信息。