大鼠噪声性听力损失后内耳及全身液体的整合蛋白质组学分析

文献信息

中文摘要

背景： 噪声性听力损失（NIHL）由急性或长期暴露于强声引起，但早期诊断仍然困难，因为部分个体在标准听力检查中仅表现出极小变化。本研究首次对急性噪声暴露后Sprague-Dawley大鼠的外淋巴、耳蜗来源脑脊液（CSF）、全血和血浆进行比较性质谱蛋白质组学分析，以识别NIHL的分子特征。方法：大鼠在麻醉下暴露于110 dB噪声1小时，经耳蜗神经复合动作电位（CAP）测得约40 dB的阈值偏移。采用数据非依赖采集（DIA）模式的纳升LC-MS/MS，随后进行肽段和蛋白质水平过滤，在外淋巴中鉴定出310种蛋白质，CSF中396种，血液中1688种，血浆中281种。差异表达分析分别揭示50、79、281和49种显著变化的蛋白质。结果：观察到共同的炎症反应，以IGHM在所有液体中一致上调为突出表现。耳蜗样本显示代谢和损伤相关蛋白富集，包括PGAM2和ALDOA，而全身样本显示纤维蛋白原链、IGFBP5和载脂蛋白的变化。KEGG通路分析提示代谢、免疫和脂质调节通路的参与。靶向PRM验证确认了所选蛋白质的变化。结论：这些发现表明对噪声创伤存在协调的局部和全身反应，支持外周生物标志物用于NIHL早期检测的潜力。

英文摘要

Noise-induced hearing loss (NIHL) arises from acute or prolonged exposure to loud sounds, yet early diagnosis remains difficult as some individuals show minimal changes in standard audiometry. This study presents the first comparative mass spectrometry-based proteomic analysis of perilymph, cochlear-derived cerebrospinal fluid (CSF), whole blood, and plasma in Sprague-Dawley rats following acute noise exposure, to identify molecular signatures of NIHL. Rats were exposed to 110 dB noise for 1 h under anesthesia, inducing an approximately 40 dB threshold shift measured by cochlear nerve Compound Action Potential (CAP). Nano LC-MS/MS in data-independent acquisition (DIA) mode followed by peptide- and protein-level filtering, identified 310 proteins in perilymph, 396 in CSF, 1688 in blood, and 281 in plasma. Differential expression analysis revealed 50, 79, 281, and 49 significantly changed proteins, respectively. A shared inflammatory response was observed, highlighted by consistent upregulation of IGHM across all fluids. Cochlear samples showed enrichment of metabolic and injury-related proteins, including PGAM2 and ALDOA, while systemic samples exhibited changes in fibrinogen chains, IGFBP5, and apolipoproteins. KEGG pathway analysis indicated involvement of metabolic, immune, and lipid-regulatory pathways. Targeted PRM validation confirmed selected protein changes. These findings demonstrate coordinated local and systemic responses to noise trauma, supporting the potential of peripheral biomarkers for early NIHL detection.