尿石素A减轻噪声性听力损失并与耳蜗线粒体自噬标志物增加相关
Urolithin A Attenuates Noise-induced Hearing Loss and Is Associated With Increased Cochlear Mitophagy Markers.
文献信息
| PMID | 42957222 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Sung Il Cho |
| 作者单位 | Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju, Republic of Korea; chosi@chosun.ac.kr. |
| 期刊 | In vivo (Athens, Greece) |
| SCI 分区 | Q3 |
| IF | 1.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景/目的： 噪声性听力损失（NIHL）是感音神经性听力损害的常见原因，其中线粒体功能障碍发挥关键致病作用。线粒体自噬对于维持线粒体质量控制至关重要。本研究探讨已知的线粒体自噬诱导剂尿石素A（UA）是否对NIHL具有保护作用。
材料与方法： 将8周龄CBA/J小鼠分为三组：对照组、噪声+生理盐水组和噪声+UA组（10 mg/kg）。通过暴露于宽带噪声（100 dB SPL，2小时）诱导NIHL。在噪声暴露前后腹腔注射UA。采用听性脑干反应（ABR）评估听觉功能。通过Western印迹、实时定量PCR、线粒体DNA（mtDNA）完整性分析、ATP测定以及免疫组织化学/免疫荧光评估线粒体自噬相关标志物和线粒体功能。
结果： 与未治疗组相比，UA治疗显著降低了听阈偏移。UA治疗组中线粒体自噬相关蛋白和基因（包括PINK1、Parkin和BNIP3）的表达水平显著升高。此外，UA在噪声暴露后恢复了ATP水平。免疫组织化学和免疫荧光分析显示，UA治疗组耳蜗（包括Corti器和螺旋神经节）中线粒体自噬体和线粒体自噬溶酶体的形成增强。
结论： UA通过增强线粒体自噬相关标志物并保护耳蜗线粒体功能来减轻NIHL。这些发现提示，药理学激活线粒体自噬可能是NIHL的一种有前景的治疗策略。
英文摘要
BACKGROUND/AIM: Noise-induced hearing loss (NIHL) is a prevalent cause of sensorineural hearing impairment, in which mitochondrial dysfunction plays a key pathogenic role. Mitophagy is essential for maintaining mitochondrial quality control. This study investigated whether urolithin A (UA), a known mitophagy inducer, protects against NIHL.
MATERIALS AND METHODS: Eight-week-old CBA/J mice were divided into three groups: control, noise + saline, and noise + UA (10 mg/kg). NIHL was induced by exposure to broadband noise (100 dB SPL, 2 h). UA was administered intraperitoneally before and after noise exposure. Auditory function was evaluated using auditory brainstem response (ABR). Mitophagy-associated markers and mitochondrial function were assessed by Western blotting, quantitative real-time PCR, mitochondrial DNA (mtDNA) integrity analysis, ATP measurements, and immunohistochemistry/immunofluorescence.
RESULTS: UA treatment significantly reduced auditory threshold shifts compared with the untreated group. The expression levels of mitophagy-related proteins and genes, including PINK1, Parkin, and BNIP3, were significantly increased in the UA-treated group. In addition, UA restored ATP levels following noise exposure. Immunohistochemical and immunofluorescence analyses demonstrated enhanced formation of mitophagosomes and mitophagolysosomes in the cochlea, including the organ of Corti and the spiral ganglion, in the UA-treated group.
CONCLUSION: UA attenuates NIHL by enhancing mitophagy-associated markers and preserving mitochondrial function in the cochlea. These findings suggest that pharmacological activation of mitophagy may represent a promising therapeutic strategy for NIHL.