Sun Jianbin, Sai Na, Zhang Tong, Tang Chaoying, Fan Shuhang, Wang Qin, Liu Da, Zeng Xianhai, Li Juanjuan, Guo Weiwei, Yang Shiming, Han Weiju
Senior Department of Otorhinolaryngology Head and Neck Surgery, The 6th Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, State Key Laboratory of Hearing and Balance Science, National Clinical Research Center for Otorhinolaryngologic Diseases, Beijing 100048, China; Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology, Xi'an 710004, China.
Senior Department of Otorhinolaryngology Head and Neck Surgery, The 6th Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, State Key Laboratory of Hearing and Balance Science, National Clinical Research Center for Otorhinolaryngologic Diseases, Beijing 100048, China.
Neurobiol Dis. 2025 Jan;204:106768. doi: 10.1016/j.nbd.2024.106768. Epub 2024 Dec 16.
Repeated low-intensity noise exposure is prevalent in industrialized societies. It has long been considered risk-free until recent evidence suggests that the temporary threshold shift (TTS) induced by such exposure might be a high-risk factor for hearing loss. This study was conducted to further investigate the manner in which repeated low-intensity noise exposure contributed to hearing damage. Two-month-old C57BL/6 J mice were exposed to white noise at 96 dB SPL for 8 h per day over 7 days to induce TTS. Auditory brainstem response (ABR) was monitored to assess changes in hearing thresholds, tracking the effects of noise exposure until the mice reached 12 months of age. Our results indicated that noise-exposed mice exhibited accelerated age-related hearing loss spanning from high to low frequencies. Proteomics analysis revealed an upregulation in the receptor for the advanced glycation end-products (RAGE) signaling pathway, which was associated with an activated inflammatory response, vascular injury, and mitochondrial and synaptic dysfunction. Further analysis confirmed increased levels of inflammatory cytokines in the cochlear lymph fluid and significant macrophages infiltration in the cochlear lateral wall, accompanied by hyperpermeability of the blood-labyrinth barrier. Additionally, degenerated mitochondria in the outer hair cells and decreased synaptic ribbons in the inner hair cells were also observed. These pathological changes indicated that noise exposure damages the cochlear cellular components, increasing the cochlear susceptibility to age-related stress. Our findings suggest that TTS caused by repeated low-intensity noise exposure correlates with a severe sensorineural hearing loss during aging; targeting the RAGE signaling pathway may be a promising strategy to mitigate damage from low-intensity noise and slow down the progression of age-related hearing loss.
在工业化社会中，反复暴露于低强度噪声的情况很普遍。长期以来，人们一直认为这种暴露是无风险的，直到最近有证据表明，由此引起的暂时性阈移（TTS）可能是听力损失的一个高风险因素。本研究旨在进一步探究反复低强度噪声暴露导致听力损伤的方式。将2月龄的C57BL/6 J小鼠每天暴露于96 dB SPL的白噪声中8小时，持续7天以诱导TTS。监测听觉脑干反应（ABR）以评估听力阈值的变化，追踪噪声暴露的影响直至小鼠达到12月龄。我们的结果表明，噪声暴露小鼠表现出从高频到低频的与年龄相关的听力损失加速。蛋白质组学分析显示晚期糖基化终产物受体（RAGE）信号通路上调，这与炎症反应激活、血管损伤以及线粒体和突触功能障碍有关。进一步分析证实耳蜗淋巴液中炎症细胞因子水平升高，耳蜗外侧壁有明显的巨噬细胞浸润，同时伴有血迷路屏障的高通透性。此外，还观察到外毛细胞中线粒体退化以及内毛细胞中突触带减少。这些病理变化表明噪声暴露会损害耳蜗细胞成分，增加耳蜗对与年龄相关应激的易感性。我们的研究结果表明，反复低强度噪声暴露引起的TTS与衰老过程中严重的感音神经性听力损失相关；针对RAGE信号通路可能是减轻低强度噪声损伤并减缓与年龄相关听力损失进展的一种有前景的策略。
