A preliminary study of the mechanism of compound hearing loss caused by ototoxic drugs combined with impulse noise  

作　　者：Xin Qiu Qing‐qing Jiang Wei‐wei Guo Ning Yu Shi‐ming Yang 

机构地区：[1]Senior Department of Otolaryngology Head and Neck Surgery,Chinese PLA General Hospital,Chinese PLA Medical School,Beijing,China [2]State Key Laboratory of Hearing and Balance Science,Beijing,China [3]National Clinical Research Center for Otolaryngologic Diseases,Beijing,China [4]Key Laboratory of Hearing Science,Ministry of Education,Beijing,China [5]Beijing Key Laboratory of Hearing Impairment Prevention and Treatment,Beijing,China [6]Chinese PLA Medical School,Beijing,China

出　　处：《iLABMED》2024年第1期38-52,共15页智能检验医学（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Number:81470700;Beijing Municipal Natural Science Foundation,Grant/Award Number:7222185;Key R&D program of Ministry of Science and Technology,Grant/Award Number:2022YFC2402704;National Key Research and Development Program of China,Grant/Award Numbers:2020YFC2004001,2020YFC2005203。

摘　　要：Background:Hearing loss(HL)is becoming increasingly common and is more commonly caused by noise,ototoxic substances,or a combination of ototoxic factors.However,so far,few studies have examined the mechanism by which compound factors cause HL.The only relevant study is about occupational ototoxic substances combined with environmental noise at 85-110 dB SPL.In this study,to address the shortcomings of existing research,we innovatively focused on HL induced by loud noise(impulse noise,>160 dB SPL)combined with common ototoxic drugs.The aim of this study was to establish and validate a mature animal model,and then to compare the characteristics of audiology,pathomorphology and molecular features,and to preliminarily predict pathogenesis in compound HL.Materials and Methods:We selected guinea pigs to construct in vivo HL model groups for different extents of exposure,including a blank control group,a single-drug group,a single-impulse noise group,and a compound group.The animal model of the mature compound HL group was established using gentamicin combined with impulse noise.We then performed audio-logical and pathological verification.We analyzed the auditory brainstem response(ABR),pathological morphology of the cochlea,and molecules(including important self-radicals,cytokines,and apoptosis signal trans-duction pathway proteins in the pathogenesis of drug-and noise-induced HL),compared the effect of different extents of exposure on HL,and preliminarily predict the pathogenic mechanism of compound HL.Results:Four groups of animal models were established successfully and verified by audiology and pathology.Regarding audiology,there were no sig-nificant differences in the ABR thresholds before exposure(p>0.05),but differences emerged among the groups after exposure.Notably,after 3,7,and 14 days of exposure,there were significant differences in the ABR thresholds between the compound group and both the drug and noise groups(p<0.01),and after 14 days,the HL of the compound group was much more severe(greater than the li

关 键 词：auditory brainstem response GENTAMICIN hearing loss impulse noise molecular mechanisms PATHOMORPHOLOGY 

分 类 号：R764[医药卫生—耳鼻咽喉科]