Prestin作为外毛细胞应激的情境依赖性生物标志物：整合临床前与临床证据

文献信息

中文摘要

听力损失的早期检测仍然是一项重大的临床挑战。在许多患者中，一旦纯音测听出现功能性改变，其恢复往往有限。外毛细胞（OHCs）对耳蜗放大至关重要，其损伤是多种感音神经性听力损失的共同通路。然而，能够实时反映听力损伤的可靠生物标志物仍然缺乏。Prestin是一种位于OHCs侧膜的运动蛋白，已被提出作为耳蜗应激的潜在标志物，但各项研究结果不一，其临床意义仍不确定。在这篇综述中，我们重新审视现有证据，以确定在哪些生物学和临床条件下血清prestin能提供有意义的信息。我们检查了顺铂暴露、氨基糖苷类耳毒性、噪声损伤、环糊精相关应激和年龄相关性听力损失模型的数据，以及可用的人体研究。在急性损伤模型中，循环prestin在早期OHC膜损伤期间常显示短暂升高，提示它反映活跃的细胞应激。相反，慢性退行性疾病和衰老与耳蜗prestin表达降低相关，这代表OHC储备的逐渐丧失而非持续的膜损伤。检测平台、异构体检测和采样时间的差异可能导致结果不一致。总体而言，prestin不应被视为听力损失严重程度的标志物。相反，它可能在特定情境下指示急性OHC膜应激。当根据病因和时机进行解读时，它可能有助于识别早期耳蜗应激，并可能在选定情况下支持更早的监测或耳保护干预。

英文摘要

The early detection of hearing loss remains a major clinical challenge. In many patients, once functional changes become evident on pure-tone audiometry, their recovery is limited. Outer hair cells (OHCs) are essential for cochlear amplification, and their injury is a common pathway in many forms of sensorineural hearing loss. However, reliable biomarkers that reflect hearing impairment in real-time are still lacking. Prestin, a motor protein located in the lateral membrane of OHCs, has been proposed as a potential marker of cochlear stress, but findings across studies vary, and its clinical significance remains uncertain. In this review, we re-examine current evidence to determine under which biological and clinical conditions serum prestin provides meaningful information. We examined data from models of cisplatin exposure, aminoglycoside ototoxicity, noise injury, cyclodextrin-related stress, and age-related hearing loss, along with available human studies. In acute injury models, circulating prestin often shows a transient increase during early OHC membrane damage, suggesting that it reflects active cellular stress. In contrast, chronic degenerative conditions and aging are associated with reduced cochlear prestin expression, which represents a gradual loss of OHC reserve rather than ongoing membrane injury. Differences in assay platforms, isoform detection, and sampling timing may contribute to inconsistent findings. Overall, prestin should not be viewed as a marker of hearing loss severity. Rather, it may indicate acute OHC membrane stress in specific contexts. When interpreted according to etiology and timing, it may help identify early cochlear stress and may support earlier monitoring or otoprotective intervention in selected settings.