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绵羊模型中声创伤后外淋巴代谢组学特征的即时早期改变

Immediate-Early Modifications to the Metabolomic Profile of the Perilymph Following an Acoustic Trauma in a Sheep Model.

作者信息

Boullaud Luc, Blasco Hélène, Caillaud Eliott, Emond Patrick, Bakhos David

机构信息

ENT Department and Cervico-Facial Surgery, CHU de Tours, 2 Boulevard Tonnellé, 37044 Tours, France.

INSERM U1253, iBrain, University of Tours, 10 Boulevard Tonnellé, 37000 Tours, France.

出版信息

J Clin Med. 2022 Aug 10;11(16):4668. doi: 10.3390/jcm11164668.

DOI:10.3390/jcm11164668
PMID:36012907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9409969/
Abstract

The pathophysiological mechanisms of noise-induced hearing loss remain unknown. Identifying biomarkers of noise-induced hearing loss may increase the understanding of pathophysiological mechanisms of deafness, allow for a more precise diagnosis, and inform personalized treatment. Emerging techniques such as metabolomics can help to identify these biomarkers. The objective of the present study was to investigate immediate-early changes in the perilymph metabolome following acoustic trauma. Metabolomic analysis was performed using liquid chromatography coupled to mass spectrophotometry to analyze metabolic changes in perilymph associated with noise-induced hearing loss. Sheep ( = 6) were exposed to a noise designed to induce substantial hearing loss. Perilymph was collected before and after acoustic trauma. Data were analyzed using univariate analysis and a supervised multivariate analysis based on partial least squares discriminant analysis. A metabolomic analysis showed an abundance of 213 metabolites. Four metabolites were significantly changed following acoustic trauma (Urocanate ( = 0.004, FC = 0.48), S-(5'-Adenosyl)-L-Homocysteine ( = 0.06, FC = 2.32), Trigonelline ( = 0.06, FC = 0.46) and N-Acetyl-L-Leucine ( = 0.09, FC = 2.02)). The approach allowed for the identification of new metabolites and metabolic pathways involved with acoustic trauma that were associated with auditory impairment (nerve damage, mechanical destruction, and oxidative stress). The results suggest that metabolomics provides a powerful approach to characterize inner ear metabolites which may lead to identification of new therapies and therapeutic targets.

摘要

噪声性听力损失的病理生理机制尚不清楚。识别噪声性听力损失的生物标志物可能会增进对耳聋病理生理机制的理解,实现更精确的诊断,并为个性化治疗提供依据。代谢组学等新兴技术有助于识别这些生物标志物。本研究的目的是调查声创伤后外淋巴代谢组的早期即时变化。采用液相色谱-质谱联用技术进行代谢组学分析,以分析与噪声性听力损失相关的外淋巴代谢变化。选用6只绵羊,使其暴露于可导致严重听力损失的噪声环境中。在声创伤前后收集外淋巴。采用单变量分析和基于偏最小二乘判别分析的监督多变量分析方法对数据进行分析。代谢组学分析显示有213种代谢物。声创伤后有4种代谢物发生了显著变化(尿刊酸(P = 0.004,FC = 0.48)、S-(5'-腺苷基)-L-高半胱氨酸(P = 0.06,FC = 2.32)、胡芦巴碱(P = 0.06,FC = 0.46)和N-乙酰-L-亮氨酸(P = 0.09,FC = 2.02))。该方法能够识别与声创伤相关的新代谢物和代谢途径,这些代谢物和代谢途径与听觉损伤(神经损伤、机械破坏和氧化应激)有关。结果表明,代谢组学为表征内耳代谢物提供了一种有力的方法,这可能有助于识别新的治疗方法和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/1e388431571d/jcm-11-04668-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/580ba4938db0/jcm-11-04668-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/b4b290e49086/jcm-11-04668-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/1e388431571d/jcm-11-04668-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/580ba4938db0/jcm-11-04668-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/b4b290e49086/jcm-11-04668-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9409969/1e388431571d/jcm-11-04668-g003.jpg

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Relationship between Metabolomics Profile of Perilymph in Cochlear-Implanted Patients and Duration of Hearing Loss.人工耳蜗植入患者外淋巴液代谢组学特征与听力损失持续时间的关系。
Metabolites. 2019 Nov 1;9(11):262. doi: 10.3390/metabo9110262.
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