miR-21介导的凋亡-坏死转化在噪声性毛细胞损伤中的作用机制研究

强噪声引起的内耳毛细胞死亡（凋亡/坏死）是引起永久性阈移的病理基础，细胞坏死会进一步激发耳蜗炎性反应，引起毛细胞继发性死亡。研究发现，miR-21可以抑制细胞凋亡并参与调控多种炎性信号通路和炎性因子的释放。我们前期研究发现，耳蜗内miR-21表达下调能够降低强噪声引起的毛细胞坏死/凋亡比例，推测miR-21可能参与了调控噪声性毛细胞损伤的病理进程。本项目拟利用噪声性聋模型进行全面而系统的研究：1）抑制内源性miR-21表达对噪声性聋的保护作用机制；2）抑制miR-21表达对内耳炎性微环境的影响；3）miR-21调控噪声性毛细胞凋亡/坏死转化的分子机制；4）抑制miR-21表达与抗炎药物联用对急性声损伤的作用，寻求基于microRNA调控增强噪声性聋治疗效果的可行性。本研究期望进一步阐明miR-21调控内耳毛细胞死亡方式转化的分子机制，探索急性噪声损伤分子治疗的新方法，新靶点。

Apoptosis/necrosis of inner ear hair cells induced by intense noise and secondary inflammatory reaction are the pathological basis of permanent threshold shift induced by noise. MicroRNA-21 (miR-21) can inhibit cell apoptosis and regulate the release of inflammatory signal pathways and inflammatory factors. Previous studies have shown that moderate noise can reduce the expression of miR-21 in the inner ear, increase the expression of anti-inflammatory factors, reduce hair cell necrosis and permanent threshold shift caused by subsequent high-intensity noise, suggesting that miR-21 is involved in regulating the pathophysiological process of noise-induced deafness. This project further uses the mouse model of noise-induced hearing loss to conduct a comprehensive and systematic study: 1) the protective effect of endogenous inhibition of the expression of miR-21 on noise-induced hearing loss; 2) the effect of inhibiting the expression of microRNA-21 on the inflammatory microenvironment of inner ear; 3) the regulatory role and mechanism of microRNA-21 in noise-induced hair cell apoptosis-necrosis transformation；4）Exploration of new drugs based on the regulation of the expression of miR-21. The aim of this study is to explore a new method to inhibit acute noise injury by targeting the apoptosis-necrosis of inner ear hair cells mediated by microRNA-21, and to find new targets for the prevention and treatment of noise-induced hearing loss.