顺铂诱导氧化应激引起耳蜗血管纹周细胞线粒体途径的细胞凋亡北大核心CSCD

目的:探讨顺铂是否通过诱导氧化应激水平升高引起耳蜗血管纹毛细血管周细胞线粒体途径的细胞凋亡。方法:将20只6~8周的雄性C57BL/6J小鼠分为对照组和顺铂组;同时原代培养小鼠耳蜗血管纹周细胞并鉴定，分为对照组、顺铂组和N-乙酰半胱氨酸（N-acetylcysteine，NAC）+顺铂组。听性脑干反应（ABR）检测小鼠听力变化，苏木精-伊红（HE）染色观察小鼠耳蜗血管纹形态学变化，总超氧化物歧化酶（superoxide dismutase，SOD）活性检测试剂盒（WST-1法）和硫代巴比妥酸（thiobarbituric acid，TBA）法分别检测SOD活性和丙二醛（malondialdehyde，MDA）含量，DCFH-DA荧光探针检测周细胞上活性氧的含量，Hoechst 33342和流式细胞术检测周细胞的凋亡率，免疫荧光技术检测耳蜗血管纹上周细胞的凋亡相关蛋白分布表达，免疫组化和蛋白免疫印迹法（WB）检测凋亡相关蛋白、线粒体相关蛋白的表达，Mito SOX TM-red和JC-1检测周细胞线粒体功能，伊文思蓝染色观察血迷路屏障（blood labyrinth barrier，BLB）的通透性。采用SPSS 18.0软件进行统计分析。 结果:与对照组相比，顺铂组可升高小鼠听力阈值和Ⅰ波潜伏期（ t值为4.72和12.25， P值均<0.05），升高耳蜗和周细胞内氧化应激水平（ t=38.34， P<0.01），使耳蜗血管纹结构紊乱皱缩，BLB通透性增加［伊文思蓝渗漏（1.08±0.42）AU比（0.55±0.23）AU， t=4.64， P<0.05］，差异均有统计学意义。顺铂组小鼠耳蜗血管纹细胞凋亡蛋白c-Caspase-3和Bax的表达增加（ t值为5.01和6.33， P值均<0.01），且顺铂可使原代培养的周细胞凋亡并上调c-Caspase-3、Bax的表达（ P值均<0.05），NAC+顺铂组可逆转顺铂诱导的周细胞凋亡（ P<0.05）。顺铂使周细胞线粒体功能损伤，诱导线粒体向胞浆释放凋亡诱导因子（apoptosis-inducing factor，AIF）和细胞色素C（cytochrome-c，Cyt-c），NAC+顺铂组可逆转顺铂诱导的线粒体损伤（ P值均<0.05）。 结论:顺铂可升高耳蜗内氧化应激水平引起C57BL/6J小鼠耳蜗血管纹周细胞线粒体途径凋亡，从而提高BLB的通透性，造成听力损失。     

高胆红素血症新生儿血清胆红素水平与听力损失程度的相关性分析

目的：探讨高胆红素血症新生儿听力损失程度与血清胆红素水平的相关性。方法对70例足月出生、体重正常、确诊为高胆红素血症的新生儿进行血清胆红素水平及听性脑干反应（ABR）检测，并对其血清胆红素水平、黄疸出现时间与ABR反应阈进行相关性分析。结果70例患儿中ABR反应阈正常17例，异常53例，其中重度听力损失27例；当血清胆红素＜342μmol／L时，黄疸出现时间≤48小时组出现重度听力损失的比例高于黄疸出现时间＞48小时组（P＜0．05），而血清胆红素值≥342μmol／L时，黄疸出现时间≤48小时组与＞48小时组轻中度、重度听力损失者比例无明显差异。ABR反应阈异常的53例患儿中，血清胆红素水平与ABR反应阈呈正相关（r＝0．041），而黄疸出现的时间与ABR反应阈呈负相关（r＝－0．291）。结论高胆红素血症新生儿黄疸出现的时间越早听力损伤的可能性越大，血清胆红素值越高听力损失程度越重。     

KCNQ1在小鼠耳蜗血管纹的表达及在听觉中的意义

目的探讨KCNQ1在耳蜗侧壁血管纹的表达及其在听觉中的作用。方法以不同基因型小鼠KC-NQ1-/-(突变纯合子)、KCNQ1 /-(杂合子)和KCNQ1 / (野生型)以及C57BL/6J小鼠为实验对象,采用免疫组织化学和ABR检测技术,检测KCNQ1在小鼠耳蜗血管纹的表达及其听力。结果KCNQ1蛋白阳性颗粒集中在小鼠耳蜗血管纹边缘细胞顶膜。KCNQ1 / 小鼠的听力正常,短声ABR的阈值为36.67±7.13dBSPL;KCNQ1 /-小鼠听力低于同窝KCNQ1 / 野生型鼠,短声ABR的阈值为38.25±9.35dB SPL;KCNQ1-/-小鼠呈现全聋,ABR在100dB SPL时仍无反应。结论KCNQ1是位于耳蜗侧壁血管纹边缘细胞的重要通道蛋白,在维系耳蜗听觉功能中有重要作用。KCNQ1通道蛋白的缺失或功能受限可以不同程度地影响耳蜗的听觉功能。     

复方丹参抗耳蜗外毛细胞凋亡的实验观察

目的 探讨氨基甙类抗生素所致耳蜗外毛细胞凋亡与听力损害关系及复方丹参对其凋亡发生的影响。方法 对35只豚鼠行药物造模,测试ABR阈值,TUNEL技术观察耳蜗外毛细胞凋亡发生情况。结果 正常豚鼠耳蜗外毛细胞无凋亡发生,耳毒性药物应用1d,3d后耳蜗各转外毛细胞均可出现凋亡阳性染色,中药干预组动物耳蜗外毛细胞凋亡数目相对较少,此外,豚鼠ABR阈值皆无明显升高。结论 耳毒性药物可诱发耳蜗外毛细胞发生凋亡;复方丹参能够对抗凋亡发生;凋亡发生早期对豚鼠听力阈值无明显影响。     

NMF308nmf/nmf小鼠耳蜗毛细胞凋亡方式及z-VAD-FMK对毛细胞的保护作用

目的 了解年龄相关性听力损失小鼠耳蜗毛细胞的凋亡方式,探讨半胱氨酸蛋白酶(caspase)抑制剂z-VAD-FMK[z-Val-Ala-Asp(Ome)-fluoromethylketone]防治老年性聋的效果。方法选用新生NMF308nmf/nmf小鼠14只和成年同窝NMF308nmf/nmf小鼠32只,分为新生小鼠腹腔注射组(14只)、成年小鼠腹腔注射组(14只)和成年小鼠圆窗膜注射组(18只),各组又分为治疗组(注射z-VAD-FMK)和对照组[注射二甲基亚枫(dimethylsulfoxide,DMSO)],采用圆窗膜局部和腹腔注射两种方法给药,给药前后行ABR检测,用免疫荧光染色化学技术TUNEL、caspase-3和PI(碘化丙啶)染色标记耳蜗毛细胞,观察各组耳蜗毛细胞的凋亡和存活状况。结果NMF308nmf/nmf小鼠从1月龄开始发生听力减退和毛细胞功能改变,到2月龄时,caspase-3激活表达的毛细胞凋亡现象是毛细胞凋亡出现的最早表现;TUNEL阳性标记特征稍晚出现;PI标记可见毛细胞细胞核固缩和碎片出现的时间从2月龄开始;到3月龄时该种小鼠听力基本丧失,耳蜗毛细胞严重缺失;而应用z-VAD-FMK治疗后,各治疗组小鼠ABR反应阈明显好于对照组;耳蜗毛细胞凋亡数目较对照组减少,存活数明显较对照组多,尤以圆窗膜注射组明显。结论 NMF308nmf/nmf小鼠耳蜗毛细胞的死亡方式以caspase-3凋亡途径为主,应用caspase-3抑制剂zVAD-FMK定向内耳给药,可以阻断caspase-3信号途径激活所导致的毛细胞凋亡,从而有效防治老年性聋。     

耳蜗性听力损失对ABR参数的影响

为了解耳蜗听力损失对ABR诸参数的影响，本文通过对40例（48耳）的平坦型、高频型、切迹型听力损失三组不同听力曲线图的耳蜗性听力损失，其ABR诸参数与正常对照组比较分析，得出高频型听力损失组Ⅰ、Ⅲ、Ⅴ各波潜伏期均较正常对照组明显延长，波间间期无明显差异；切迹型听力损失组V波及Ⅰ-Ⅴ波间期轻度延迟，但无显著意义；平坦型听力损失组与正常对照组无显著差异。实验结果提示：耳蜗性听力损失的类型对ABR诸参数有一定影响，因此，临床上应用ABR诊断蜗后病变时需考虑这些因素的存在。     

一氧化氮对庆大霉素耳毒性的影响

目的研究耳蜗内不同水平的一氧化氮(NO)含量对庆大霉素(GM)耳毒性的影响.方法将实验动物豚鼠随机分为GM组;庆大霉素加左旋精氨酸(GM加L-Arg)组;庆大霉素加NG-单甲基-L-精氨酸(GM加L-NMMA)组和正常对照组.实验过程中观察动物体重变化,检测ABR反应阈;取标本检测血清和耳蜗组织NO含量,耳蜗铺片观察毛细胞损失程度.结果对照组动物体重增加明显,各实验组体重增加缓慢,其中GM加L-Arg组体重略有下降.实验第4周,GM加L-Arg组ABR反应阈升高明显,与GM组比较有统计学意义(P<0.05),GM加L-NMMA组ABR反应阈升高较少,与GM组比较有统计学意义(P<0.05).GM加L-Arg组血清和耳蜗NO含量明显升高,GM加L-NMM A组NO含量升高不明显,与GM组比较差异具有显著性(P<0.05).耳蜗铺片各组毛细胞损失程度与ABR变化相对应.结论增加耳蜗NO含量可增加GM耳毒性,减少耳蜗NO含量可减轻GM耳毒性.     

庆大霉素暴露对小鼠肾脏与耳蜗功能损伤效应的对应关系研究

目的观察氨基糖甙类药物庆大霉素进入小鼠肾脏和耳蜗毛细胞在时间和数量上的特点及肾功能和听功能损害情况。方法将18只6周龄的C57小鼠随机分为3组,分别为对照组(contr)、用药后1天组(d1)、用药后7天组(d7),每组6只动物。置备完成的Texas Red标记庆大霉素(GTTR)以100mg/kg浓度腹腔注射小鼠,1次/天,通过激光共聚焦显微镜观察荧光标记庆大霉素在各组小鼠耳蜗毛细胞和肾脏组织积蓄情况,采用Image-Pro Plus软件测算标本荧光强度值,并进一步估算各标本庆大霉素摄取情况。同时,通过生化检测和听力检测,观察用药后小鼠肾功能和听功能损害情况。结果小鼠标本荧光强度(OD)值测算结果:用药后1天,小鼠肾脏组织中庆大霉素即达到了高水平,P<0.01;与此同时,小鼠耳蜗毛细胞内虽然检测到明显的红色荧光,但是其OD值要明显低于肾脏组织。用药后7天,肾脏组织和耳蜗毛细胞的OD值均比对照组有极为显著的升高(P<0.01)。对小鼠肾功能和听力的检测显示,用药后1天小鼠血液中BUN和Scr水平即有明显升高,表明此时肾功能已受到损害;而用药后1天小鼠ABR阈值和对照组相比却未见显著升高(P>0.05),表明此时听力损害尚未显现。在用药后7天,小鼠BUN、Scr和ABR阈值水平和对照组相比均有显著改变(P<0.01)。结论和肾功能损害相比,庆大霉素对小鼠听觉损害具有时间上的滞后效应,而这种时间上的延迟反应为听力损害的临床干预提供了可能。     

严重高胆红素血症新生儿的听力学特征

目的探讨严重高胆红素血症新生儿的听力学特点及其与血清总胆红素浓度峰值的相关性。方法对100名严重高胆红素血症新生儿(研究组)和30名正常新生儿(对照组)进行畸变产物耳声发射(DPOAE)、听性脑干反应(ABR)和1 000 Hz探测音声导抗检查,于3月龄和6月龄时对研究组进行复查。比较两组结果并分析患儿血清总胆红素浓度峰值与ABR反应阈的相关性。结果①对照组ABR、DPOAE、声导抗检查均正常;②研究组中所有患儿鼓室导抗图均为A型,15人22耳有不同程度的听力损失(ABR异常),其中6人(40%,6/15)9耳DPOAE不能引出,9人(60%,9/15)13耳DPOAE引出。3月龄复查时,15人中听力损失改善3人(4耳),加重1人(2耳),6月龄复查时与3月龄时无改变;③研究组血清总胆红素浓度峰值与ABR反应阈呈浓度依赖性正相关,血清总胆红素>500μmol/dl是高胆红素致听力损失的风险因素。结论严重新生儿高胆红素血症导致的听力损失表现为单耳或双耳感音神经性聋,部分表现为听神经病的听力学特点,3～6月龄部分听力损失可逆转,部分听力损失可继续加重。     

年龄相关听力损失BALB／c小鼠耳蜗形态学观察

目的 探讨年龄相关听力损失小鼠耳蜗毛细胞形态学变化,建立年龄相关听力损失动物模型.方法 分别取3、6、12、18月龄BALB/c小鼠测定其听性脑干反应(ABR)阈值,应用耳蜗铺片和扫描电镜技术,观察不同月龄鼠耳蜗毛细胞计数和形态的变化.结果 3、6、12月龄鼠8 kHz ABR反应阈分别为(24.8±5.1)、(51.5±6.7)和(92.5±7.5)dB SPL.18月龄组120 dB SPL刺激声无诱发反应.耳蜗铺片毛细胞计数自6月龄组外毛细胞出现显著缺失,随月龄增加而加重,由底回逐渐向顶回发展,至12月龄时耳蜗底回和中回外毛细胞几乎完全丧失,内毛细胞显著缺失.扫描电镜显示6月龄组小鼠耳蜗毛细胞静纤毛可见不同程度的缺失、转位、散乱、倒伏、融合、变短现象,随月龄增加而逐渐加重.结论 BALB/c小鼠听力损失、耳蜗毛细胞缺失和纤毛损害随年龄增加而逐渐加重,可作为年龄相关听力损失研究的合适动物模型     

Effects of antioxidants on the aging inner ear

Age-related cochlear structural changes include the degeneration of sensory, neural cells and the stria vascularis. The hypothesis that cellular degeneration results from exposure to oxidative products of respiration was tested by supplementing aged dogs with a diet high in antioxidants and mitochondrial metabolites and by genetically modifying the expression level of the antioxidant, manganese superoxide dismutase (SOD2) in mice. Aged dogs received either a high antioxidant diet or a normal, control diet for the last 3 years of their life. Cellular measures were compared among the two aged groups (10-15 years) and young dogs. Both aged groups had cellular degeneration relative to young dogs, but the animals fed the antioxidant diet showed less degeneration at the base and apex than the control-diet group. Transgenic mice, heterozygous null for SOD2, produce only half as much enzyme as a normal mouse. These mice showed no increase in the amount of hearing loss relative to the background strain. A diet containing antioxidants reduced the magnitude of cochlear degeneration. Genetic reduction of one antioxidant, however, did not increase the magnitude of hearing loss in aging mice. A reduction in one enzyme seems to be compensated while the addition of a complex of factors is effective.     

Comparative analysis of serum homocysteine, folic acid and Vitamin B12 levels in patients with noise-induced hearing loss

OBJECTIVE: The aim of the present study was to determine the levels of homocysteine, folic acid, and Vitamin B12 in subjects with noise-induced hearing loss. Furthermore, possible links between these parameters and noise-induced hearing loss were aimed to be evaluated. METHODS: In the present study, blood samples were obtained from all subjects after overnight fasting for biochemical analysis. We examined the levels of homocysteine, Vitamin B12 and folic acid levels in subjects with noise-induced hearing loss. Twenty-eight male patients with noise-induced hearing loss (mean age 37 +/- 5 year) were included in the study group whereas the control group was composed of 32 healthy male volunteers (mean age 36 +/- 4 year). RESULTS: It was found that homocysteine levels of subjects with noise-induced hearing loss as significantly high compared to healthy controls (P < 0.05). On the other hand, Vitamin B12 and folic acid levels of patients with noise-induced hearing loss were determined to be significantly low compared to the controls (P < 0.05 and < 0.01, respectively). CONCLUSION: Our findings indicate that there might be a link between increased homocysteine levels and noise-induced hearing loss. Since increased homocysteine levels cause elevated levels of free radicals in addition to its atherogenic and thrombogenic effects. Further experimental studies are needed to decipher how this relationship is linked.     

Changes in the cochlear iron enzymes and adenosine triphosphatase in experimental iron deficiency

The influences of iron deficiency on the cochlear iron enzymes and adenosine triphosphatase were studied in 68 iron-deficient rats and 68 control rats (normal and with chronic anemia). A disorderly or topographic distribution and reduction or disappearance of the cochlear succinic dehydrogenase and peroxidase reaction products were found in 37.8% of the rats fed on a basic iron-deficient diet for 14 to 100 days. The activity of cochlear sodium-potassium-dependent adenosine triphosphatase in iron-deficient rats was slightly increased, compared to that in normal controls. These results suggest that iron deficiency would produce significant abnormalities of succinic dehydrogenase and peroxidase activity, which in turn would disturb cell respiration and initiate peroxidative damage to the inner ear cells, result in sensorineural hearing loss, or provide a pathologic basis for cochlear deafness.     

Age-Related Hearing Impairment and B Vitamin Status

The aim of this study was to examine, in elderly subjects, a possible association between age-related hearing impairment and vitamin B₁₂ or folic acid status. Ninety-one consecutive subjects with pure age-related hearing impairment, 35 males and 56 females, with a median age of 78 years, range 67-88 years, were included in the investigation. All subjects underwent a thorough evaluation, including pure-tone, speech and impedance audiometry. Blood samples were drawn for determination of B₁₂, folic acid and homocysteine and analysed by routine laboratory measurements. No significant differences in the blood parameters as a function of gender could be demonstrated and no correlations were found between B₁₂ or folic acid and hearing levels averaged across the range 0.5-4 kHz. A weak correlation between hearing levels and homocysteine (r=0.03; correlation coefficient 0.004) was found; however, a comparison of the hearing levels between those with increased and normal homocysteine failed to show any significant differences. In addition, no association between B₁₂ and the speech recognition score could be found. This investigation therefore fails to demonstrate any association between hearing level and vitamin B₁₂ or folic acid in elderly subjects.     

缺铁性贫血治疗前后听性脑干反应的变化

目的 :探讨缺铁性贫血导致感音神经性聋的治疗方法及疗效。方法 :将 6 8只 Wistar大鼠分成 3组 :48只通过缺铁饮食制作缺铁性贫血模型 ,缺铁 A组和 B组各 2 4只 ;另设标准对照 C组正常大鼠 2 0只。将 A、B两组进行缺铁饲养 6周 ,检测听性脑干反应 (ABR) ,每组各随机取样 10只检测畸变产物耳声发射 (DPOAE) ,再分别给予铁剂加高压氧治疗和单纯铁剂治疗。结果 :缺铁 Wistar大鼠经 6周饲养 ,较实验前 ABR听觉阈值提高和 波 PL 延长 ,经过两种不同方案治疗 6周 ,均取得明显效果 (P<0 .0 5 ) ,但两组差异无显著性。结论 :对于缺铁性贫血造成感音神经性耳聋 ,早期给予及时的铁剂治疗疗效好 ,而高压氧用于治疗此类耳聋并非必要。     

Age-related hearing impairment and B vitamin status

The aim of this study was to examine, in elderly subjects, a possible association between age-related hearing impairment and vitamin B12 or folic acid status. Ninety-one consecutive subjects with pure age-related hearing impairment, 35 males and 56 females, with a median age of 78 years, range 67-88 years, were included in the investigation. All subjects underwent a thorough evaluation, including pure-tone, speech and impedance audiometry. Blood samples were drawn for determination of B12, folic acid and homocysteine and analysed by routine laboratory measurements. No significant differences in the blood parameters as a function of gender could be demonstrated and no correlations were found between B12 or folic acid and hearing levels averaged across the range 0.5-4 kHz. A weak correlation between hearing levels and homocysteine (r = 0.03; correlation coefficient 0.004) was found; however, a comparison of the hearing levels between those with increased and normal homocysteine failed to show any significant differences. In addition, no association between B12 and the speech recognition score could be found. This investigation therefore fails to demonstrate any association between hearing level and vitamin B12 or folic acid in elderly subjects.     

Steroid treatment in young MRL.MpJ-Fas(lpr) autoimmune mice prevents cochlear dysfunction.

Corticosteroid therapy reverses clinical autoimmune sensorineural hearing loss, although little is known of how steroids restore normal auditory function. If suppression of systemic autoimmune processes underlies hearing restoration, then preventing autoimmune symptoms from developing should prevent cochlear dysfunction. MRL. MpJ-Fas(lpr) autoimmune mice were used to test this potential mechanism by initiating oral prednisolone treatment at 6 weeks of age, prior to autoimmune disease and hearing loss onset. The steroid treatment group was given prednisolone in their drinking water, while untreated controls were given tap water. Treatment continued for 7 months with periodic evaluations of cochlear function with auditory brainstem response (ABR) audiometry. Autoimmune mice given the steroid lived longer and did not develop levels of serum immune complexes seen in their untreated controls. Also, their ABR thresholds remained near normal throughout the 7 months of treatment, while untreated controls showed progressive threshold elevations typical for autoimmune disease. This correlation of suppressed systemic autoimmune activity and maintenance of normal cochlear function identifies one potential mechanism for autoimmune hearing loss and hearing restoration with steroid therapy. The autoimmune mouse should serve as a valuable model for future studies of the cochlear mechanisms responsive to steroid treatment in autoimmune hearing loss.     

Vitamin D-deficient diet rescues hearing loss in Klotho mice

Klotho-deficient mice exhibit a premature aging syndrome, a feature of which is mild hearing loss. In the present study, the hearing phenotype of Klotho mice was characterized to better determine how well this phenotype resembles presbycusis in humans. It was demonstrated that Klotho animals have auditory-evoked brainstem response (ABR) threshold shifts of 14-18 dB in response to pure tone stimuli of 4, 8, 16 and 32 kHz, and similarly, in response to clicks; however, cochlear histology and spiral ganglion neuron density appeared normal in these mice. It was further demonstrated that a vitamin D-deficient diet normalizes serum calcitriol (1,25(OH)(2)D(3)) levels and prevents hearing loss in Klotho mice. It is concluded that hearing loss in Klotho mice is caused by elevated renal 1α-hydroxylase expression and consequent excessive production of calcitriol. These findings implicate the vitamin D metabolic pathway in hearing loss and pose questions as to the mechanism by which elevated calcitriol levels mediate such hearing loss.     

Auditory System Dysfunction due to Infantile Thiamine Deficiency: Long-Term Auditory Sequelae

Eleven infants who were fed a thiamine-deficient formula for a mean of 3 months were evaluated for immediate and long-term auditory abnormalities. At presentation, 8 infants had auditory neuropathy spectrum disorder (ANSD), which resolved with supplementary thiamine in 5 children, was permanent in 2 children, and deteriorated in 1 patient who died at the age of 7 years. An additional patient had an auditory pattern corresponding to that of auditory neuropathy of brain stem origin. The 2 remaining patients had unilateral cochlear hearing loss. Six to 8 years later, all patients with transient ANSD had normal audiograms, 2 patients had unilateral cochlear hearing loss, and the rest had neural hearing loss. All survivors had a language developmental delay and impaired speech intelligibility of varying degrees, especially in the presence of background noise. Thiamine is crucial for normal auditory development and function, and its deficiency may be considered an acquired metabolic cause of ANSD in infants.     

Rat hearing loss and hearing organs mitochondrial DNA4834 deletions associated with hypercholesteremia]

OBJECTIVE: To determine whether or not the rat hypercholesteremia contributes to hearing organs mtDNA4834 deletion and involves in the development of hearing loss. METHODS: The rat hypercholesteremia model (n = 38) was established by feeding with high cholesterol diet and the control group (n = 22) with common diet for 6 months. The rats were tested for auditory sensitivity using auditory brainstem response (ABR). Twenty-one left cochleae and 27 left cochlear nuclei from experimental group and 10 left cochleae and 13 left cochlear nuclei from control group were harvested. The total DNA of them was extracted. mtDNA was amplified by nest PCR to examine the presence of mtDNA4834 deletion. RESULTS: Our result showed: (1) There is a significant increase in serum cholesterol level and ABR threshold in the experimental group. (2) The mitochondrially-encoded tRNA and ND1 segments were amplified from all samples, as well as mtDNA4834 deletions. (3) The incidence of mtDNA4834 deletions in hearing organs of hypercholesteremia rats was significantly higher than that of the control group (P < 0.05). CONCLUSION: Extended hypercholesteremia can induce hearing loss, and mtDNA4834 deletion in hearing organs may be one of the pathogenic mechanisms.