5-磷酸二酯酶抑制剂对噪声性聋影响的实验研究

目的探讨5-磷酸二酯酶(PDE5)抑制剂对豚鼠噪声性聋的影响。方法豚鼠随机数字表法分为对照组、噪声暴露组和西地那非给药组,每组15只。西地那非组及噪声组豚鼠在白噪声暴露1周后分别腹腔注射西地那非10mg/(kg.d)及生理盐水4 ml/(kg.d),连续给药4周。分别测试噪声暴露前1天、噪声暴露后1、2及4周听性脑干反应(ABR)阈值及80dB HL下ABRⅠ波潜伏期,并通过扫描电镜观察噪声暴露后4周豚鼠耳蜗毛细胞的形态变化。结果与噪声暴露前相比,西地那非组ABR阈值及Ⅰ波潜伏期均小于噪声组,差异具有统计学意义(P值均<0.01)。扫描电镜显示,噪声组豚鼠耳蜗内、外毛细胞均出现听毛紊乱、融合及缺失;而西地那非组耳蜗病变较轻,听毛仅有轻微倒伏、融合现象。结论西地那非能够减轻噪声对豚鼠耳蜗毛细胞的损害,降低噪声性听觉损伤引起的ABR阈值升高,缩短其引起的Ⅰ波潜伏期延长。     

依达拉奉对豚鼠耳蜗急性声损伤的保护作用

目的 探讨自由基清除剂依达拉奉对豚鼠耳蜗急性声损伤的保护作用.方法 48只白色红目雌性豚鼠随机分为6组.A组(空白对照组):不做任何处置,单纯检测听功能和耳蜗自由基含量;B组:鼓室注射生理盐水;C组:鼓室注射依达拉奉;D组:单纯噪声暴露;E组:噪声暴露+静脉注射依达拉奉;F:噪声暴露+鼓室注射依达拉奉.D、E、F组在声压级125 dB的稳态噪声暴露前2 d及暴露2 h后即刻、2、6、12、24、48和72 h检测听功能和耳蜗自由基含量.听功能检测为听性脑干反应(ABR),自由基检测采用电子顺磁共振(electron spin resonance,ESR)技术.比较各组动物在不同时间点ABR阈移及自由基含量的变化.结果 急性声损伤后豚鼠ABR阈值明显升高,与空白对照组比较,差异具有统计学意义(P<0.05),暴露后72 h仍未恢复正常.鼓室注射依达拉奉可使阈值下降约10 dB,而静脉注射则无此作用.空白对照组豚鼠耳蜗自由基值为21.68(cm/g),急性声损伤后耳蜗自由基含量明显增加,在噪声暴露后2 h达峰值,至观察结束时仍未恢复正常.静脉注射依达拉奉组对噪声损伤后耳蜗自由基生成未见明显抑制作用,而鼓室注射组则可明显抑制自由基产生.结论 经鼓室局部应用依达拉奉,对豚鼠急性声损伤后的耳蜗听觉功能具有保护作用,其机制可能与有效清除局部自由基有关.     

天麻素对噪声性耳蜗损伤防护作用的实验研究

目的观察天麻提取液-天麻素对噪声性耳蜗损伤的防护作用.方法豚鼠28只随机分成3组,正常组8只、噪声组10只和天麻素组10只,暴露于噪声的同时加用天麻素.所有豚鼠均作ABR、耳蜗基底膜铺片和扫描电镜观察.结果噪声组(64.37dB)和天麻素组(31.25dB)ABR阈值均显著高于正常组(20dB),但天麻素组显著低于噪声组(P＜0.01).天麻素组耳蜗毛细胞和静纤毛损害均轻于噪声组.结论天麻素能降低豚鼠噪声暴露后的ABR阈值,减轻毛细胞损害,对噪声性耳蜗损伤有防护作用.     

噪声暴露后豚鼠耳蜗电生理和超微结构的改变

目的 观察豚鼠噪声暴露后其耳蜗电生理与毛细胞超微结构的改变,探讨哺乳动物在毛细胞受损后能否自我修复.方法 将30只豚鼠分为四组,正常对照组5只,噪声暴露后0.5 h组5只,7天组10只,3周组10只,后三组豚鼠暴露于 120 dB SPL白噪声中2 h,分别于结束暴露后0.5 h及7天、3周后检测听性脑干反应(auditory brainstem response, ABR)及40 Hz听觉相关电位(40 Hz-AERP),扫描电镜观察耳蜗超微结构的变化.结果 豚鼠噪声暴露后7天组、3周组ABR及40 Hz-AERP较0.5 h组有所恢复,但未恢复至正常水平,差异仍具有统计学意义.扫描电镜观察噪声暴露后耳蜗毛细血管内的红细胞随时间延长逐渐增加,外毛细胞倒伏现象有改善.结论 噪声暴露后外毛细胞可能有自我修复功能.     

用于毛细胞再生研究的噪声性聋动物模型的建立

目的观察高强度脉冲噪声暴露后豚鼠听功能及耳蜗结构的变化,探讨用于毛细胞再生研究的噪声性聋动物模型的建立方法。方法健康成年白色红目豚鼠50只,雌雄不限,体重250～300g。随机分成2组,正常对照组10只,噪声暴露组40只。给予脉冲噪声（压力峰值为175．0dB SPL,脉宽0．25ms,间隔时间20秒）连续暴露200次。于噪声暴露前及暴露后1周、4周、8周检测听性脑干反应（auditory brainstem respons,ABR）,毛细胞计数及耳蜗铺片免疫组化观察耳蜗结构变化。结果高强度脉冲噪声暴露后1周,40只豚鼠中有21只（52．5％）双耳各频率ABR阈值≥95dBSPL。继续观察至噪声暴露后4周及8剧,ABR阈值没有恢复,1周、4周、8周各频率ABR阈值比较无统计学差异（P〉0．05）。毛细胞计数结果显示,噪声暴露敛极重度聋后1周,内毛细胞平均缺失率为91．4％,外毛细胞平均缺失率为97．2％。免疫组化染色分析结果显示,噪声暴露致聋后1周,内、外毛细胞胞核大部分缺失,内毛细胞内侧及外毛细胞外侧的支持细胞的胞核存存。结论高强度脉冲噪声暴露可造成豚鼠极重度感音神经性聋,耳蜗毛细胞广泛缺失且无法内行恢复,而支持细胞夫部分仔留,是进行毛细胞再生研究的理想动物模型。     

NGB基因转染拮抗庆大霉素耳毒性作用的实验研究

目的验证阳离子脂质体介导脑红蛋白(neuroglobin,NGB)基因转染对庆大霉素致豚鼠耳毒性的保护作用。方法将ABR反应阈均不超过40dB SPL的120只健康花色豚鼠随机分为5组,每组24只:Ⅰ组:空白对照组;Ⅱ组:人工外淋巴液对照组(经左耳注入人工外淋巴液);Ⅲ组:人工外淋巴液实验组(经左耳注入人工外淋巴液后肌肉注射庆大霉素);Ⅳ组:空质粒转染组(经左耳注入空质粒pEGFP-C1后肌肉注射庆大霉素);Ⅴ组:NGB基因转染组(经左耳注入pEGFP-NGB后肌肉注射庆大霉素),庆大霉素均经后腿肌肉注射120mg.kg-1.d-1,共给药14天。停止给药后喂养14天,各组均行ABR检测,耳蜗基底膜铺片、免疫组化观察各组豚鼠耳蜗基底膜毛细胞形态学及NGB蛋白表达的变化。结果给药后Ⅰ组ABR反应阈平均为37.22dB SPL(左耳)和36.94dB SPL(右耳),Ⅱ组阈值平均为37.22dB SPL(左耳)和37.50dB SPL(右耳),Ⅲ组阈值平均为119.44dB SPL(左耳)和122.22dB SPL(右耳);Ⅳ组阈值平均为119.72dB SPL(左耳)和120.83dB SPL(右耳);Ⅴ组阈值平均为83.89dB SPL(左耳)和100.56dB SPL(右耳)。Ⅴ组ABR反应阈较Ⅰ组和Ⅱ组显著升高(P<0.05),较Ⅲ组和Ⅳ组显著降低(P<0.05)。Ⅴ组中手术耳ABR反应阈较非手术耳降低(P<0.05)。耳蜗基底膜铺片示Ⅰ组和Ⅱ组内外毛细胞排列整齐,无缺失,Ⅲ组和Ⅳ组内外毛细胞极少量残存,其中ABR阈值大于135dB SPL的豚鼠耳蜗毛细胞几乎消失殆尽,Ⅴ组毛细胞部分缺失,且主要是外毛细胞;免疫组织化学染色示Ⅴ组耳蜗毛细胞NGB蛋白表达量较其余各组均显著增高(P<0.05),其余各组几乎均未见明显阳性表达。结论本研究成功验证了阳离子脂质体介导NGB基因转染对庆大霉素致豚鼠耳毒性具有有效的保护作用。     

两种内淋巴给药方式对豚鼠耳蜗功能和形态的影响

目的 观察经耳蜗侧壁打孔(侧壁径路)和经圆窗膜、基底膜穿刺(双膜径路)两种内淋巴系统给药方式对豚鼠耳蜗整体形态结构和功能的影响并比较两种方式的优劣.方法 40只正常健康杂色豚鼠分为A、B两组(每组20只),所有动物左侧为给药耳,右侧为非给药耳.A组采用侧壁径路进入中阶灌注携带增强型绿色荧光蛋白基因的5型重组腺病毒(adenovirus5-enhanced green fluorescence protein,AdS-EGFP)5 μl;B组采用双膜径路进入中阶灌注AdS-EGFP 5μl.给药前后行听性脑干反应(ABR)测试,观察听功能改变.耳蜗冰冻切片直接荧光观察腺病毒分布,HE染色观察手术径路的愈合情况.基底膜铺片鬼笔环肽染色观察毛细胞受损情况,扫描电镜观察局部损害情况.结果 所有动物术后均存活.穿刺部位修复良好,耳蜗的完整性得以保持.EGFP在Corti器和血管纹内壁细胞内标记明显,表明两种给药径路都可以将药物成功注入内淋巴系统.A组证实成功14只(70%),手术前后ABR反应阈(声压级)变化[(33.1±10.3)dB]与对侧非给药耳[(9.4±3.9)dB]比较差异具有统计学意义(F=46.34,P=0.0005);B组证实成功8只(40%)手术前后阈值改变[(2.5±3.8)d8]与对侧耳[(2.5±3.8)dB]比较差异无统计学意义(F=0.00,P=1.000).两种方法在部分动物中都有药物渗漏入外淋巴的现象,给药局部产生炎性反应,侧壁径路对毛细胞的损害范围大于双膜径路.结论 两种手术径路都可将药物成功注人豚鼠耳蜗的内淋巴系统中,局部有炎性反应,术后耳蜗的完整性可以获得完全恢复.侧壁径路对豚鼠耳蜗毛细胞缺失和ABR反应阈的影响大于双膜径路,但是经侧壁径路进入中阶的手术成功率高于双膜径路,选择何种灌注径路需要根据实验要求来定.     

豚鼠老化模型听反应阈检测及基因多态性标记分析

目的 建立D-半乳糖致豚鼠老化模型,应用扩增片段长度多态性(amplified fragment length polymorphism,AFLP)分析检测与听力损失相关的分子生物学标记,寻求老年性聋发病的分子机制.方法 51只豚鼠随机分为三组:A组(模型实验组)21只,5%D-半乳糖腹腔注射(200 mg·kd-1·d-1),共6周;B组(模型对照组)15只,仅给予生理盐水注射.A、B两组注射前后分别进行听性脑干反应(ABR)检测,将两组豚鼠置于噪声环境中7 d,每天噪声暴露8 h,结束后再次检测ABR阈值.C组(空白对照组)15只,不加任何处理,仅予以同步检测ABR阈值.用比色法检测三组肝和脑组织的超氧化物歧化酶(superoxide dismutase,SOD)及丙二醛(maleic dialdehyde,MDA)含量.提取三组豚鼠内耳组织DNA,应用AFLP技术筛选差异位点.结果 注射后A组豚鼠ABR阈值较B组提高,但两组阈移之间差异无统计学意义(t=1.14,P>0.05),噪声暴露后,A组ABR阈值(峰等效声压级)平均提高(22.97±10.56)dB,B组提高(14.16±7.36)dB,组间差异具有统计学意义(t=2.78,P<0.05).A组肝和脑组织中SOD活性明显低于B组,MDA含最则明显高于B组,其差异具有统计学意义(P值均<0.01).AFLP分析发现有与耳聋一致的多态性标记.结论 D-半乳糖可以诱导豚鼠衰老,此模型豚鼠听反应阈虽无明显提高,但对噪声的敏感性增加,AFLP检测到的差异位点可能与其对噪声敏感有关.     

噪声对豚鼠耳蜗基底膜乙酰化组蛋白H2B表达的影响

目的 观察噪声性聋豚鼠耳蜗基底膜毛细胞乙酰化组蛋白H2B表达水平的变化,探讨组蛋白乙酰化与噪声性听力损失的相关性.方法 成年雄性白色红目豚鼠60只随机分为噪声组和对照组,两组豚鼠分别进行听性脑干反应(ABR)检测后,噪声组给予高强度窄带噪声(122 dB SPL,3小时)暴露,对照组不予任何处理;噪声组于噪声暴露后1小时、3天、7天、14天和21天分别行ABR检测;并以免疫荧光染色和Western blot方法检测两组豚鼠耳蜗基底膜听觉细胞中乙酰化组蛋白H2B的表达水平.结果 噪声暴露后1小时、 3天、7天、14天、21天噪声组豚鼠ABR各频率反应阈均较噪声暴露前及对照组显著增高,且随时间的延长听力逐渐恢复,14天时趋于稳定,达到永久性阈移.免疫荧光染色显示在噪声组豚鼠耳蜗内外毛细胞及Hensen's细胞中乙酰化组蛋白H2B荧光强度较正常对照组减弱,Western blot结果显示噪声组豚鼠耳蜗基底膜中乙酰化组蛋白H2B的表达(H2B-AcK5/β-actin比值为0.310 2±0.083 9)较对照组(0.617 9±0.126)明显下调,两组差异有统计学意义(P<0.01).结论 噪声可导致豚鼠内耳感觉细胞乙酰化组蛋白H2B表达水平下降,乙酰化组蛋白失衡有可能参与了噪声性聋的发生.     

MK-801对噪声性听力损伤保护作用的研究

目的:观察N 甲基 D 天冬氨酸(NMDA)受体的非竞争性拮抗剂MK 801在声损伤中对暂时性阈 移(TTS)或永久性阈移(PTS)的保护作用。方法:将40只豚鼠平均分为两组,分别暴露于倍频程噪声(4kHz中 心频率)110dBSPL3h或115dBSPL5h。取110dB或115dB豚鼠各10只(药物组)在噪声暴露前和后立即 给予MK 801(0.5mg/kg体重,腹腔内注射);另各10只豚鼠(对照组)在相同的时间给予等体积的生理盐水腹腔 内注射。测试暴露前后听性脑干反应(ABR)的阈值,透射电镜观察毛细胞及传入神经末梢的形态。结果:110 dB药物组和对照组动物在噪声暴露后立即测试TTS,两组差异无统计学意义(P>0.05);1周后两组阈移都消 失。115dB药物组暴露后1周阈移明显低于对照组(P<0.05);暴露后3周,该药物组残留的PTS仍显著低于 对照组(P<0.01)。经超微结构检查,110dB药物组和对照组的毛细胞及传入神经末梢正常;115dB药物组内 毛细胞及传入神经末梢结构正常,对照组内毛细胞及传入神经末梢空泡变性。结论:MK 801对TTS缺乏保护, 对PTS有部分的保护作用。这种保护作用须通过预防内毛细胞及传入神经末梢空泡变性来实现。     

Potentiation of noise-induced hearing loss by amikacin in guinea pigs.

Noise and aminoglycosides initially attack cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are used for the early diagnosis of damage to OHCs. The effects of sub-damaging doses of amikacin, an aminoglycoside antibiotic agent, on noise-induced hearing loss (NIHL) were examined in guinea pigs. Animals were grouped by gender and exposed to broadband noise at 105 dB SPL for 12 h and/or injected i.m. with either amikacin (100 mg/kg/day) or saline for 10 days. Auditory brainstem response (ABR) thresholds, along with DPOAE amplitudes, were measured serially before and after noise exposure. DPOAE amplitudes decreased and ABR thresholds elevated immediately after noise exposure and then gradually recovered. At all frequencies, the emission amplitudes recovered completely to pre-exposure baseline values by 4 days after noise exposure. There was no effect of amikacin on either the ABR threshold or DPOAE amplitudes, in animals treated with amikacin only. However, amikacin significantly prolonged the effect of noise exposure on DPOAE amplitude but not on the noise-induced temporary threshold shift (TTS) of the ABR. In animals treated with a combination of noise and amikacin, significant changes in DPOAE amplitudes were still observed at 4 weeks after cessation of noise exposure. No gender difference in the responses to noise and/or amikacin could be demonstrated. The present findings indicate that even sub-damaging dosages of amikacin might impair recovery from NIHL in guinea pigs.     

高频听力损失对豚鼠低频区时间分辨率的影响

目的 构建豚鼠高频听力损失模型,通过听觉惊跳反射前抑制方法观察高频听力损失后,低频区时间分辨率的变化.方法 采用简单随机法将豚鼠分为实验组(6只)和对照组(4只),实验组暴露于声压级110 dB的12 kHz纯音下30 h,建立8 kHz以上听力损失模型,对照组未作处理.于噪声暴露前、暴露后2周、4周、6周及8周等五个时间点进行听觉惊跳反射前抑制试验和听觉脑干反应(ABR)测试.在听觉惊跳反射前抑制试验中,选用0.5～2 kHz,0.5～4 kHz和0.5～8 kHz三种背景噪音频率(均在听敏度正常的低频段)来观察低频区时间分辨率的变化.结果 噪声暴露后2周,实验组动物呈现8 kHz以上频率陡降型高频听力损失,在16 kHz、32 kHz和48 kHz频率均有平均55 dB的阈移,与声暴露前相比差异均有统计学意义(P值均＜0.05),而1 kHz、2 kHz、4 kHz和8 kHz在噪音暴露前后差异均无统计学意义(P值均＞0.05).在8周的实验期内,实验组高频听力损失仍然存在.对照组豚鼠所有频率的听敏度在实验期内各个时间点差异均无统计学意义(P值均＞0.05).实验组在8 kHz的背景噪音下,声暴露后第2周抑制能力减弱,与暴露前相比差异具有统计学意义(P=0.036),其余时间点和暴露前相比差异无统计学意义(P值均＞0.05);在4 kHz的背景噪音下,声暴露后所有时间点的抑制能力与暴露前相比差异均无统计学意义(P值均＞0.05);在2 kHz的背景噪音下,声暴露后第6周、第8周抑制能力降低,与暴露前相比差异具有统计学意义(P值均＜0.05).结论 高频听力损失可降低正常低频区的时间分辨率.

Abstract：

Objective To constitute the animal model of high frequency hearing loss and observer the temporal processing abilities of low frequency regions using prepulse inhibition of auditory startle response (gap-PPI).Methods Ten guinea pigs were randomly grouped into two groups: the high frequency hearing loss group with six guinea pigs and the control group with four guinea pigs.The former group was exposed to 12 kHz tone at 110 dB SPL for 30 hours to establish the high frequency hearing loss above 8 kHz and the latter group received no stimuations.Before and two,four,six and eight weeks after noise exposure,gapPPI and auditory brainstem response (ABR) were recorded in both groups.In the gap-PPI experiment,three different background noises as 0.5-2 kHz,0.5-4 kHz and 0.5-8 kHz were applied to test the temporal gap.Results High frequency hearing loss above 8 kHz was shown two weeks after noise exposure.The averaged ABR thresholds of 16 kHz,32 kHz and 48 kHz were elevated about 55 dB and shown statistical significance compared to those before exposure (P ＜ 0.05＝.No significant difference of ABR thresholds were shown between 1 kHz,2 kHz,4 kHz and 8kHz before and after noise exposure(P ＞0.05).In the control group,the ABR thresholds remained stable during experiment.In the gap-PPI test,two weeks after noise exposure of 8 kHz,the experiment group showed attenuated inhibition ability and recovered gradually four weeks after noise exposure.No statistical differences of inhibition ability at time points of two,four,six and eight weeks after noise exposure of 4 kHz were detected when compared with that of pre-exposure.Under the background noise of 2 kHz,the inhibition ability attenuated and reached statistical significance at 6-8 weeks after noise exposure.Conclusion The high frequency hearing loss might induce an impairment of the temporal processing in the low frequency region.     

Math1基因内耳导入后噪声性聋豚鼠听功能改变观察

目的观察Math1基因内耳导入对噪声性聋豚鼠听功能的影响,探讨Math1基因过表达对噪声损伤耳蜗的生物学效应,为内耳基因治疗提供实验基础和理论依据。方法经脉冲噪声致聋的豚鼠45只（各频率ABR阈值均≥95dB SPL）,雌雄不限,实验开始时体草250～300g。随机分为3组：Ad—Math1-EGFP组（30只）;Ad—EGFP组（5只）;空白组（10只）。各组豚鼠在基因转导后4周、8周分别测试双耳ABR。测试完毕后处死动物,观察听泡及耳蜗尤炎性病变者记录听阈结果。结果Math1导入后4周,导入耳各频率ABR阈值低于对照耳（右耳）,也低于Ad—EGFP组及空内组,平均达到85dBSPL。Math1导入后8周,导入耳各频率ABR阂值低于对照耳（右耳）,也低于Ad—EGFP组及空白组,与4周时比较,进一步好转,平均达到75dB SPL。结论Math1基因内耳导入可使噪声导致全聋的豚鼠听功能部分恢复,为噪声性聋的治疗打开了新的思路和手段。     

水杨酸钠对噪声性听力损失影响的实验

目的 观察水杨酸钠能否减轻噪声引起的听力损失。方法 将３６只健康且耳廓反射正常的花色豚鼠随机分为水杨酸钠实验组、生理盐水对照组、水杨酸钠对照组和噪声暴露组。噪声暴露采用１０５ｄＢ ＳＰＬ的４ＫＨｚ窄带噪声下暴露２ｈ,连续５ｄ。水杨酸钠给药为每天０．５ｇ／ｋｇ体重连续１０ｄ。由短声诱发听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓｅ,ＡＢＲ）,连续测试其阈值;而后取动物双侧耳蜗荧     

Effects of alpha-tocopherol on noise-induced hearing loss in guinea pigs

Preventing noise-induced hearing loss (NIHL) by antioxidants is based on the hypothesis that generation of reactive oxygen species is one of the causes of NIHL. alpha-Tocopherol is a naturally occurring antioxidant with no noticeable side effects. In this study, we attempted to protect guinea pigs from developing NIHL by administering alpha-tocopherol. Pigmented male guinea pigs were exposed to a noise (4 kHz octave band, 100 dB SPL), 8 h/day for 3 days consecutively. alpha-Tocopherol (10 mg/kg or 50 mg/kg daily) was given by intraperitoneal injection from 3 days before through 3 days after the noise exposure. Auditory evoked brainstem response (ABR) thresholds at 2, 4 and 8 kHz were recorded prior to the experiment, immediately post-noise, 2 and 8 days post-noise. On day 8 post-noise, after the ABR recording, guinea pigs were decapitated and the cochleae were removed for cochlear surface preparations and scanning electron microscope (SEM) study. ABR threshold shifts of groups receiving alpha-tocopherol were significantly smaller than those of groups not receiving alpha-tocopherol at all frequencies and all time points tested except that of group 3 at 8 kHz 8 days post-noise. No hair cell loss was seen on the surface preparations, but stereocilia loss was found by SEM study. The noise-induced stereocilia loss was significantly decreased by alpha-tocopherol. These results indicate that alpha-tocopherol can attenuate the noise-induced cochlear damage. Further investigations on the preventive effect of alpha-tocopherol on NIHL in noise-exposed workers are necessary.     

Effect of water-soluble coenzyme Q10 on noise-induced hearing loss in guinea pigs

Conclusion. The results of this study indicate that coenzyme Q10 reduces cochlear oxidative stress induced by acoustic overstimulation. Objective. We investigated the effects of coenzyme Q10 on noise-induced hearing loss in guinea pigs. Materials and methods. Animals received water-soluble coenzyme Q10 intraperitoneally 2 h before noise exposure. Seven days after noise exposure (130 dB sound pressure level for 3 h), the auditory brainstem response (ABR) threshold shift and cochlear hair cell damage were assessed. Results. We observed that the ABR threshold shift was significantly less in the coenzyme Q10 group than in the vehicle control group. In addition, the percentage of missing outer hair cells was lower in the coenzyme Q10 group than in the control group. Moreover, 2 days after administration of coenzyme Q10, increased antioxidative activity in the cochlea, as measured by analysis of hydroxy radical scavenging activity by electron spin resonance was observed.