噪声性聋耳蜗螺旋神经节磷酸化c-Jun活性变化

目的:通过神经损伤性噪声引起4周昆明小鼠出现暂时性阈移(TTS)和永久性阈移(PTS),探讨听觉通路N-甲基D-天冬氨酸受体(NMDAR)活性调节耳蜗螺旋神经节(CG)磷酸化c-Jun变化.方法:采用30只昆明小鼠制作噪声性聋动物模型,进行听觉脑干诱发反应听力检测,并采用免疫组织化学对耳蜗听觉通路中NMDAR关键成分(磷酸化c-Jun)的表达进行检测.结果:噪声性聋诱导PTS后8 h、48 h、7 d、14 d CG磷酸化c-Jun的相对吸收度值明显增加,而阳性细胞数依次减少.噪声性聋诱导PTS前后立即腹膜腔注射MK-801引起相似改变.而诱导TTS后48 h则降至正常水平.结论:磷酸化c-Jun在噪声性聋后表达的增加具有时间相关性;MK-801通过阻断噪声暴露后传入神经递质谷氨酸,减少突触后钙内流所致的兴奋性毒性,从而保护听觉神经.因此,NMDAR可能参与了内耳损伤.     

银杏叶提取物对噪声致大鼠螺旋神经节损伤的保护作用

目的探讨银杏叶提取物对大鼠噪声暴露后螺旋神经节损伤的保护作用。方法将36只SD大鼠分为三组：正常对照组（正常组）、生理盐水＋噪声暴露组（噪声组）、银杏叶提取物＋噪声暴露组（用药组）,每组12只。后两组大鼠每天暴露于110dBSPL白噪声中6h,连续10天,且于噪声暴露开始每天分别腹腔注射生理盐水和银杏叶提取物10ml/d。所有大鼠均于实验前和实验第10天检测听性脑干反应（auditory brainstem response,ABR）,并于第二次测试ABR后处死动物,检测耳蜗组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量,并用透射电镜观察耳蜗螺旋神经节细胞的超微结构变化。结果实验后噪声组和用药组的ABR阈值均高于正常组,但用药组显著低于噪声组,差异有统计学意义;用药组SOD活性较噪声组明显增加、MDA含量较噪声组显著降低,差异有统计学意义;用药组耳蜗螺旋神经节损害明显轻于噪声组。结论银杏叶提取物对大鼠噪声暴露后螺旋神经节细胞的损害具有保护作用。     

EGB761对脉冲所致噪声性聋大鼠内耳形态及功能影响的研究

目的探究银杏叶提取物(Ginkgo biloba extract,EGB761)对脉冲所致噪声性聋的大鼠内耳ABR阈值、毛细胞核染色、及锰超氧化物歧化酶(Manganese superoxide dismutase,Mn-SOD)活性的影响。方法 80只SD大鼠随机分为2组:空白对照组20只、实验组60只。实验组大鼠均给予声压级为150d B脉冲噪声,脉宽为30ms,重复率为1/min,连续3发。脉冲噪声暴露后随机分成暴露即刻组、生理盐水组和EGB761组。EGB761组腹腔注射金纳多4ml/kg,2/日,连续注射7天;生理盐水组腹腔注射生理盐水4ml/kg,2/日,连续注射7天。结果听觉脑干反应(Audi-tory Brain-Stem Response,ABR)结果显示噪声暴露后实验组大鼠ABR阈值显著高于暴露前,差异有统计学意义(P<0.01),各实验组大鼠间无统计学差异(P>0.05)。治疗7天后,生理盐水组及EGB761组大鼠ABR阈值均下调,EGB761组大鼠ABR阈移明显高于生理盐水组,差异有统计学意义(P<0.05)。免疫荧光结果显示空白对照组大鼠内耳底回外毛细胞细胞核排列整齐;噪声暴露即刻组大鼠内耳底回外毛细胞核排列稀疏,较正常对照组缺失明显增多,但仍以点状缺失为主;生理盐水组底回外毛细胞核缺失明显,且出现片状缺失,较暴露即刻组损伤严重;EGB761组较生理盐水组底回外毛细胞核排列稀疏散乱,但缺失明显减少,以点状缺失为主。Mn-SOD结果显示噪声暴露即刻组内耳Mn-SOD活性与空白对照组无统计学差异(P>0.05);生理盐水组Mn-SOD活性显著低于暴露即刻组,差异有统计学意义(P<0.01),EGB761组Mn-SOD活性明显高于生理盐水组,差异有统计学意义(P<0.05)。结论EGB761能明显改善脉冲所致噪声性聋的听功能下降、减少毛细胞消失及氧化应激反应,对脉冲所致噪声性聋的预后意义显著。     

内皮素1在豚鼠耳蜗螺旋神经节的分布

内皮素1是1988年日本学者 Yanagisawa从猪主动脉内皮细胞培养液中分离纯化的一种活性肽,研究发现内皮素1不仅是收缩能力最强的血管收缩物质,而且具有多种生物学活性,对气道张力形成、细胞增殖与凋亡、离子转运、基因调控等均发挥多种生物学影响,近来发现内皮素1对神经系统的生理活动亦具有调控作用.     

强噪声暴露下豚鼠耳蜗螺旋神经节细胞凋亡及Caspase-3的表达

目的探讨强噪声能否诱导豚鼠耳蜗螺旋神经节细胞（sprial ganglion cell,SGC）的凋亡及SGC的凋亡是否与凋亡蛋白酶Caspase-3信号转导有关。方法选用健康雄性白色豚鼠20只,随机分为4组,每组5只,其中3组为实验组,1组为对照组。将实验组动物暴露于4kHz、120dB SPL窄带噪声中4h,分别测试噪声刺激停止后1、4、14d及对照组豚鼠听性脑干反应（auditory brainstem response,ABR）。通过透射电镜和脱氧核糖核甘酸末端转移酶介导的缺口末端标记法（ternial-deoxynucleotidyl transferase mediated nick end labeing,TUNEL）,检测SGC凋亡细胞,免疫组织化学方法检查Caspase-3蛋白的表达。结果透射电镜观察发现实验组SGC出现了凋亡细胞的特征性改变。实验组SGC的TUNEL染色明显增强,Caspase-3的表达增高,与对照组比较差异均有显著统计学意义（P〈0.01）。结论强噪声可以诱导SGC凋亡;SGC凋亡与caspase-3的激活有关。     

中国的噪声性听力损害是一个潜在严重的公众健康问题

听力损失和耳鸣是长期噪声暴露的最常见的后果,它是大多数发展中国家将面临的严重健康问题。快速的工业化进程与人们生活方式的改变使得我国对噪声暴露和噪声诱发听力损失(NIHL)越来越关注。然而我国对NI-HL的研究仍然有限。本文回顾了我国噪声暴露及NIHL的研究,讨论了其对我国人口的影响,以及Dangerous Deci-bels?等研究模型在我国有效应用的可能性,以呼吁加强对我国公民(特别是年轻人)关于NIHL及其预防措施的科普教育工作,并提出语言文化对国际信息传播和行为干预方面的影响。     

噪声性聋小鼠耳蜗螺旋神经节生长相关蛋白-43变化

目的通过噪声引起4周龄昆明小鼠出现暂时性阈移（tmporary threshold shift,TTS）和永久性阈移（permanent threshold shift,PTS）,观察听觉通路耳蜗螺旋神经节神经元（spiral ganglion of cochlea,CG）中生长相关蛋白（growth associated protein 43,GAP-43）变化,探讨听觉损伤后内耳突触修复的可能机制。方法采用32只昆明小鼠制作噪声性聋动物模型,进行听觉脑干诱发反应听力检测,用免疫组化法对耳蜗听觉通路中GAP-43在神经损伤刺激的表达进行检测。结果噪声性聋引起PTS后CG的GAP-43表达在损伤后第7天出现增加,第14天仍增加明显,而TTS组无明显变化。结论噪声性聋听觉通路神经性损伤作用后7天,GAP-43出现增高说明内耳开始出现突触修复。     

噪声性听力损失

噪声性听力损失(Noise-induced hearing loss,NIHL)是指因患者暴露在噪声环境所引起的渐进性感音神经性聋[1].由于工业化加重、社会噪声增加和人口寿命延长,噪声性听力损失已成为重大的公共卫生问题.美国的统计数据显示,该国在6～19岁儿童和青少年人群中发病率为12.5%,在20～69岁成人中发病率为17%.职业性噪声性听力损失是职业病中最常见的,2 5%的美国工厂存在可导致听力损失的噪声,49%～70%的男性矿工在50～70岁时存在听力障碍.     

谷氨酸对体外培养螺旋神经节细胞的损伤作用

目的：探讨谷氨酸对体外原代培养的大鼠耳蜗螺旋神经节细胞（SGC）兴奋性毒性作用。方法：SGC在体外培养4d，加入1mmol／L谷氨酸，继续培养24h后，用荧光显微镜观察Annexin-V-FITC和PI双标的细胞形态改变，以及用激光共聚焦方法观察细胞内游离钙离子浓度的变化。结果：体外培养4d的SGC，用1mmol／L谷氨酸处理24h后，与对照组相比，出现大量的细胞受损，表现为死亡或凋亡（P〈0．05）；用Fluo-3染色，激光共聚焦显微镜观察，加入谷氨酸后，80％的SGC细胞内钙离子迅速增加，150s达到高峰。结论：谷氨酸诱导的SGC钙离子内流与细胞受损有明显的关系。     

脑源性神经营养因子对耳蜗螺旋神经节的保护作用

目的 观察腺疾病携带的脑源性神经营养因（brain derived neurotrophic factor,BDNF）在豚鼠耳蜗中的表达，及噪声损伤后螺旋神经节的保护作用。方法 27只白色纯豚鼠，暴露于135dBSLP，4kHz的窄带噪声4h。7d后，12只经圆注入腺病毒携带BDNF（adenoviral-mediated BDNF,ad-BDNF），12只经圆窗注入ad-LacZ,3只注入人工外淋巴液。分别于1、4、8周后取材，石蜡包埋中轴切片后，用免疫组化方法（ABC法）检测BDNF的表达。于光镜下计数螺旋神经节细胞。结果 在耳蜗各回中BDNF均有表达，4、8周组动脉较1周组织动物表达弱。在8周，注入ad-BNDF组较adLacZ组和人工淋巴组螺旋神经发生退行性病变的数目少，螺旋神经节细胞计数结果经统计学t检验，P＜0．01，差异有显著性。结论 腺病毒携带的神经营养因子在耳蜗中能高效表达，在噪声损伤情况下腺病毒携带的脑源性神经营养因子对螺旋神经节有保护作用。该研究为基因治疗感音神经性聋提供了坚实的实验基础。     

Noise-Induced Hearing Loss and Presbyacusis

The effect of aging on hearing (threshold) levels at 1 000 and 4 000 Hz was investigated in war veterans who had normal hearing for their age at 1 000 Hz and considerable hearing losses at 4 000 Hz (produced by acoustic trauma or other war-time noise exposure) when first tested audiometrically. It was found that the threshold levels at both 1 000 and 4 000 Hz had increased by approximately the amounts predicted by presbyacusis curves, in spite of the hearing losses at 4 000 Hz. The results thus support the hypothesis that presbyacusis and noise-induced hearing loss are independent and additive at 4 000 Hz.     

Measurement of Hearing Level in Occupational Noise-Induced Hearing Loss

Research on the hearing loss at 2 000 and 4 000 Hz which enabled us to estimate the loss at 3 000 Hz would appear to be the best measure of occupational noise-induced hearing loss: this measure is the most specific and the most discriminating of the suggested formulas. Calculation of the social handicap must take into consideration the same frequencies and the probability of error of identification at the various levels of hearing impairment. Its coefficient is that of the disability in relation to total deafness.

Notre recherche montre que seules les fréquences de 2 000 et 4 000 Hz, approximation de la fréquence 3 000 Hz, sont acceptables pour estimer une perte auditive professionnelle. La moyenne à ces deux fréquences est plus spécifique et plus discriminative. Le calcul de la perte sociale peut se faire à partir de la probabilité d'erreur de la discrimination phonétique, ou ces memes fréquences sont également les plus importantes.     

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl-N-tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.     

Acoustic Reflex Amplitude and Noise-Induced Hearing Loss

Acoustic reflex maximum amplitude measurements elicited both contralaterally and ipsilaterally were obtained from subjects with noise-induced hearing loss and compared with those obtained from normal-hearing subjects. The eliciting signal was a pure tone of 1 kHz presented for 1 000 ms. The groups were matched on age, sex, static immittance and ear canal volume. Acoustic reflex amplitudes were clearly reduced in noise-impaired subjects compared with normal-hearing subjects at a frequency where their hearing thresholds were normal.     

军事噪声性听力损失研究进展

军事噪声是指军事演习或战争期间的各种武器装备产生的噪声,来源包括枪炮武器的爆震声、发动机的机械声、军舰汽笛声、电机及通信设备声等.噪声因士兵所处的噪声环境不同而不同,但接触同等噪声时由于个体间的差异对噪声会有不同的反应,个体的基因组成差异也起十分重要的作用.近年来,军事噪声性耳聋在噪声特点、机制研究、易感基因、防治等方...     

Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss

Loss of auditory sensory hair cells is the major pathological feature of noise-induced hearing loss (NIHL). Currently, no established clinical therapies for prevention or amelioration of NIHL are available. The absence of treatments is due to our lack of a comprehensive understanding of the molecular mechanisms underlying noise-induced damage. Our previous study indicates that epigenetic modification of histones alters hair cell survival. In this study, we investigated the effect of noise exposure on histone H3 lysine 9 acetylation (H3K9ac) in the inner ear of adult CBA/J mice and determined if inhibition of histone deacetylases by systemic administration of suberoylanilide hydroxamic acid (SAHA) could attenuate NIHL. Our results showed that H3K9ac was decreased in the nuclei of outer hair cells (OHCs) and marginal cells of the stria vascularis in the basal region after exposure to a traumatic noise paradigm known to induce permanent threshold shifts (PTS). Consistent with these results, levels of histone deacetylases 1, 2, and 3 (HDAC1, HDAC2 and HDAC3) were increased predominately in the nuclei of cochlear cells. Silencing of HDAC1, HDAC2, or HDAC3 with siRNA reduced the expression of the target HDAC in OHCs, but did not attenuate noise-induced PTS, whereas treatment with the pan-HDAC inhibitor SAHA, also named vorinostat, reduced OHC loss, and attenuated PTS. These findings suggest that histone acetylation is involved in the pathogenesis of noise-induced OHC death and hearing loss. Pharmacological targeting of histone deacetylases may afford a strategy for protection against NIHL.     

甲硫氨酸对噪声性听力损失的预防作用研究

目的：探讨口服甲硫氨酸对噪声性听力损失的预防作用。方法将解放军某部健康男性军人203例随机分为试验组（113例）和对照组（90例）,均给予脉冲噪声（峰值160～170 dB SPL）暴露1小时,暴露前3天试验组口服甲硫氨酸片1500 mg/日×3天,对照组则口服等剂量安慰剂（淀粉）。两组受试者噪声暴露前后行纯音测听、听性脑干反应听（ABR）检查,对检查结果进行统计学分析。结果噪声暴露后1天,两组各频率纯音听阈均高于暴露前（P＜0．05或 P＜0．01）,暴露后7天,对照组纯音听阈仍升高（P＜0．05）,而试验组与暴露前比较差异无统计学意义（P＞0．05）;噪声暴露前、暴露后1天、7天,试验组 ABR 反应阈分别为40．5±9．3、51．7±12．3、44．1±11．4 dB nHL,对照组分别为41．5±8．9、62．4±13．7、47．6±12．5 dB nHL,试验组 ABR I－V 波间期分别为3．72±0．21、3．99±0．36、3．82±0．25 ms,对照组分别为3．71±0．22、4．45±0．37、3．85±0．34 ms,噪声暴露后1、7天两组间 ABR 反应阈、I－V 波间期比较差异有统计学意义（P＜0．05或 P＜0．01）。结论噪声暴露前口服甲硫氨酸片能有效减轻噪声暴露后噪声性听力损失的发生。     

噪声性耳聋相关易感基因的研究进展

噪声性耳聋(Noise-induced hearing loss,NIHL))是由于遗传与工业、军事和娱乐等环境因素相互作用所导致的一种获得性进行性感音神经性听力损伤,对于其遗传因素方面的研究,对NIHL的易感候选基因筛选主要是通过对噪声转导途径的关键酶基因等进行筛选研究,主要包括钙粘蛋白基因、氧化应激类基因、钾离子循环有关基因、热应激蛋白70、对氧磷酶200基因等其他基因。本文对目前发现的噪声性耳聋相关易感基因的研究进行了综述。     

The Questionable Relation between Cochlear Pigmentation and Noise-Induced Hearing Loss

Some evidence has suggested that susceptibility to noise-induced hearing loss may be inversely proportional to the amount of melanin in the cochlea. However, published data have not been consistent in demonstrating this relation, and some results may be contaminated by lack of genetic control in experimental animals. In this investigation, noise-induced hearing loss was evaluated in pigmented and albino C57BL/6J mice that differed only in their ability to produce melanin. Surface-recorded electric responses to sound were used to assess auditory sensitivity. Results indicated no difference between the two groups either in pre-exposure thresholds or in magnitude of noise-induced threshold shift.

Relation éventuelle entre pigmentation cochléaire et surdité due au bruit

Quelques recherches ont suggéré que la prédisposition à la réduction de sensibilité auditive provoquée par le bruit pourrait ětre inversement proportionnelle à la quantité de mélanine dans 'organe cochléaire. Cependant, les données publiées 'ont pas démontré cette relation 'une façon consistente, et il semble que certains résultats aient été contaminés par 'absence de contrôle génétique chez les animaux de laboratoire. Dans cette recherche, on a mesuré la réduction de sensibilité auditive provoquée par le bruit chez des souris albinos et pigmentées différant dans leur aptitude à produire de la mélanine. Pour établir la sensibilité auditive, on a utilisé 'enregistrement des potentiels évoqués auditifs en surface. Les résultats 'ont indiqué aucune différence entre les deux groupes, ni dans les seuils de pré-exposition ni dans Pimportance de la surdité induite par le bruit.     

Envelope Coding in Auditory Nerve Fibers Following Noise-Induced Hearing Loss

Recent perceptual studies suggest that listeners with sensorineural hearing loss (SNHL) have a reduced ability to use temporal fine-structure cues, whereas the effects of SNHL on temporal envelope cues are generally thought to be minimal. Several perceptual studies suggest that envelope coding may actually be enhanced following SNHL and that this effect may actually degrade listening in modulated maskers (e.g., competing talkers). The present study examined physiological effects of SNHL on envelope coding in auditory nerve (AN) fibers in relation to fine-structure coding. Responses were compared between anesthetized chinchillas with normal hearing and those with a mild–moderate noise-induced hearing loss. Temporal envelope coding of narrowband-modulated stimuli (sinusoidally amplitude-modulated tones and single-formant stimuli) was quantified with several neural metrics. The relative strength of envelope and fine-structure coding was compared using shuffled correlogram analyses. On average, the strength of envelope coding was enhanced in noise-exposed AN fibers. A high degree of enhanced envelope coding was observed in AN fibers with high thresholds and very steep rate-level functions, which were likely associated with severe outer and inner hair cell damage. Degradation in fine-structure coding was observed in that the transition between AN fibers coding primarily fine structure or envelope occurred at lower characteristic frequencies following SNHL. This relative fine-structure degradation occurred despite no degradation in the fundamental ability of AN fibers to encode fine structure and did not depend on reduced frequency selectivity. Overall, these data suggest the need to consider the relative effects of SNHL on envelope and fine-structure coding in evaluating perceptual deficits in temporal processing of complex stimuli.