应用卡那霉素与速尿(Furosemide)引起的耳蜗损伤

卡那霉素与利尿酸(Ethacrynic acid)同时使用,因交互作用引起永久性听力损伤者,在临床与动物实验均已证实,特别是大剂量应用时,短期内就能引起严重的永久性听力损伤。速尿与利尿酸的化学结构不同,但在肾脏内的作用颇为相似。速尿在人体引起暂时性听力损伤者已有报告,但与卡那霉素同时应用发生交互作用引起永久性耳聋者尚未见有报导。本研究之目的是通过动物实验观察二者能否产生交互作用而导致永久     

对乙酰氨基酚致小鼠听觉损伤的实验研究

目的：研究对乙酰氨基酚对小鼠听觉的影响。方法：健康7周龄C57小鼠40只，雌雄不分，随机分为4组：对乙酰氨基酚低剂量组（150mg／kg）、中剂量组（300mg／kg）、高剂量组（600mg／kg）及空白对照组（2ml生理盐水）。每组10只。观察每组于喂药第0、2、4、9天ABR反应阈，通过免疫荧光法观测耳蜗基膜毛细胞形态学改变，用高效液相色谱法测定小鼠耳蜗内淋巴液中对乙酰氨基酚浓度。结果：对乙酰氨基酚灌胃30min后，检测小鼠耳蜗内淋巴中对乙酰氨基酚的浓度，内淋巴中药物浓度与灌服剂量相关。对乙酰氨基酚各组随给药时间延长ABR听阈增高，中、高剂量组给药后9d的平均阈值分别为（44．75±16）dB、（50．00±11．00）dB，与对照组比较差异均有统计学意义（均P〈0．05）；随着灌服时间的延长，对乙酰氨基酚各组的免疫荧光镜显示内、外毛细胞出现不同程度的缺失。结论：对乙酰氨基酚可通过血迷路屏障进入内耳，服用一定剂量的对乙酰氨基酚可造成小鼠听力损伤。     

利尿酸是打开血-迷路屏障的钥匙

目的观察在不同的时机应用利尿酸以暂时破坏耳蜗血管纹上皮是否能够开放血-迷路屏障,从而促使庆大霉素进入耳蜗或者从耳蜗排出.方法听神经动作电位测试技术,全耳蜗毛细胞计数定量观察技术和荧光偏振免疫法测定庆大霉素浓度的技术被用于以下两个不同目的的实验观察.(1)当庆大霉素血中浓度高于内耳液浓度时,应用利尿酸破坏蜗管外壁以促使更多的庆大霉素进入耳蜗以制备不同程度耳蜗损害的动物模型.(2)当庆大霉素内耳浓度高于血中浓度时,应用利尿酸损坏蜗管外壁以促使蓄积在耳蜗内的庆大霉素从内耳排出以达到挽救毛细胞的目的.结果1.当庆大霉素血中浓度高于内耳液浓度时,注射利尿酸可造成更多的毛细胞损害和听功能障碍,外淋巴中药物的峰值浓度和半衰期浓度也均比单独一次注射庆大霉素动物外淋巴中药物浓度增加一倍,说明同时注射利尿酸可促使更多的庆大霉素从血液进入耳蜗并造成更严重的毛细胞损害.2.当血液中庆大霉素排空之后,注射利尿酸可减少毛细胞数量的损失程度,同时发现延迟注射利尿酸组动物的听力损失程度比不经利尿酸处理动物组有所减轻,外淋巴中药物浓度也比不经利尿酸处理动物组降低一半,说明当GM在耳蜗内蓄积但血清中已经排空时注射EA有助于降低药物在耳蜗内的蓄积并挽救尚未被破坏的毛细胞.结论利尿酸可以做为打开血-迷路屏障的钥匙,但是应用利尿酸开放血-迷路屏障可以产生双向结果,其关键在于注射利尿酸的时机.     

实验性链脲佐菌素糖尿病性聋动物模型制备的研究

目的探讨建立合适的实验性糖尿病性聋动物模型的方法。方法应用Wistar大鼠经阴茎静脉注射不同剂量链脲佐菌素(streptozotocin，STZ)诱导建立实验性糖尿病性聋动物模型，观察实验动物血糖、尿糖、体重及听性脑干反应变化情况。结果STZ 40mg／kg组动物糖尿病成模率仅为22％，且成模动物饲养3个月后仍无听力损害情况出现。而STZ 55mg／kg组及65mg／kg组动物糖尿病成模率分别可达94％及95％，且糖尿病成模后2月起即有听力损害情况。至成模后3个月，听力损害情况更进一步加重。STZ 65mg／kg组动物死亡率极高。结论实验显示我们建立的实验性链脲佐菌素糖尿病性聋动物模型是成功的，55mg／kg的STZ剂量为诱导实验性糖尿病性聋大鼠模型、并用于较长期观察研究的适宜剂量。     

灰鼠畸变产物耳声发射改变和外毛细胞缺失程度的相关分析

目的 探讨灰鼠畸变产物耳声发射(DPOAE)幅值的降低与外毛细胞缺失率之间的关系.方法 联合应用顺铂和利尿酸钠,建立灰鼠耳蜗毛细胞损伤模型.12只灰鼠在静脉注射利尿酸钠(40 mg/kg)同时,腹腔注射顺铂(0.2 mg/kg),分别于用药前和用药后的1周、2周及3周在清醒状态下检测动物DPOAE,并在施行最后1次DPOAE检测后处死动物.常规制备灰鼠耳蜗基底膜铺片并进行全耳蜗毛细胞计数.计算用药前和处死前DPOAE幅值的改变程度,通过Pearson相关分析对DPOAE幅值的降低与外毛细胞缺失程度之间的相关性进行分析.结果 顺铂和利尿酸钠引起灰鼠耳蜗外毛细胞缺失的特点是病变始发于基底膜的底回并逐渐向顶回发展,外毛细胞的缺损程度沿着基底膜从底回向顶回逐渐减轻,而不同频率DPOAE幅值降低的程度亦遵循从高频向低频发展的规律,各频率DPOAE在注射顺铂和利尿酸钠后的幅值改变与基底膜上相应部位的外毛细胞缺损程度存在一定的对应关系(r=0.796,P<0.05).外毛细胞每损失1%,可引起约0.24 dB的DPOAE幅值降低.结论 在灰鼠耳蜗损伤模型中,从DPOAE幅值的变化可以大致评估耳蜗外毛细胞的缺失程度.     

消炎痛拮抗卡那霉素耳毒作用的实验研究

为研究消炎痛对卡那霉素耳毒性的拮抗作用,本实验用听力正常的健康花斑豚鼠60只,分两组,KF组用卡那霉素450mg/kg ip及速尿60mg/kg iv,观察8天;KFI组用卡那霉素450mg/kgip,速尿60mg/kg iv,半小时后用消炎痛10mg/kg iv,第2-8天继续用消炎痛5mg/kg/d ip。两组动物于用卡那霉素、速尿前及用药后第8天检测ABR,CAP,最后一次检测听功能后,在扫描电镜及光镜下观察耳蜗螺旋器及血管纹。发现KF组ABR(Ⅲ)及CAP(N_1)声反应阈阈值较KFI组明显提高(P<0.05),耳蜗毛细胞出现程度不同的形态学变化,血管纹无水肿。结果提示,消炎痛可减轻卡那霉素的耳毒性。     

实验性注入速尿和verospiron时耳蜗淋巴离子组成的变化

近年来利尿剂速尿和verospiron等的耳毒性作用已引起重视。但利尿剂中毒的机制还未充分研究。本文研究应用速尿和verospiron时在猫的耳蜗外淋巴、血清和脑脊液中K~ 、Na~ 和Ca~ 离子浓度的动力学变化。以28只体重平均为2～3 kg的雄或雌性猫作试验。第一组(6只)作为对照组。第二组(5只)接受了中毒剂量的(20mg/kg)速尿行腹腔内注射,一日两次,连用7天。第三组(5只)注入治疗剂量的(5 mg/kg)速尿,一日两次,腹腔内注射,连用15天。第四组(6只)行腹腔内注射中毒剂量的(5 mg/kg)verospiron,一日两次,共用7天。第五组(6只)以同样的方式注射治疗剂量的(2.5mg/     

紫杉醇对豚鼠听阈的影响

目的：探讨紫杉醇对豚鼠听阈的影响。方法：将30只雌性豚鼠随机分为6组（1个对照组和5个实验组,每组5只）,实验组分别予以不同剂量紫杉醇腹腔内注射,检测用药前、后各组动物ABR阈值。结果：实验组听力水平用药后均显著减低,相关分析显示,总药量与听力损失程度之间无显著相关性。结论：紫杉醇可导致轻到中度听力损失。     

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。     

C57BL/6J小鼠在不同剂量氨基糖甙类药物暴露下听力损害的特点

目的探讨C57BL/6J小鼠在不同剂量氨基糖甙类药物毒性作用下听力损害的特点。方法采用不同剂量的庆大霉素对成年C57BL/6J小鼠进行腹腔注射,小鼠随机分成五组,药物剂量浓度分别为300mg/kg,200mg/kg,100mg/kg和50mg/kg。对照组为等量的注射用0.9%生理盐水,药物注射连续应用7天。分别于用药前(p0,对照组)以及用药后第2天(P2)、第4天(P4)、第7天(P7)检测动物的听功能(Click&Tonebrust),并进组间差异的比较分析。结果 (1)在50mg/kg组,用药后第7天的听阈值和对照组听阈分别为48.33±10.33(P7)和41.67±11.20(P0),两者相比具有显著性差异(P<0.05)。在100mg/kg组,用药后第4天的听阈值和对照组相比具有显著性差异(P4:48.89±9.16;P0:40.83±10.07,P<0.05)。在200mg/kg和300mg/kg组,用药后第2天的听阈值和对照组相比有显著上升(200mg/kg,P2:50.56±5.39;P0:40.42±9.66,P<0.05),(300mg/kg,P2:50.50±6.85,P0:40.00±11.00,P<0.05)。(2)各剂量组药物在Click和Toneburst(4kHz,8kHz&t16kHz)频率中,听力损害程度存在区别,损害程度依次为:200mg/kg组>300mg/kg组>100mg/kg组>50mg/kg组。(3)在8kHz&16kHz频率上,①50mg/kg与300mg/kg剂量组在给药后第2、4、7天均无明显听力变化(P>0.05)。②在100mg/kg组:与对照组相比,给药后第4天、第7天的听阈出现明显升高(P<0.05)。③在200mg/kg组:给药后第2、4、7天的听阈值亦出现显著升高(P<0.05)。(4)在给药后第7天,各剂量组的听阈均达到峰值。结论本研究表明:(1)随着给药剂量的增加,C57BL/6J小鼠听力损害出现的时间提前,但听力损害的程度并非同步加重;(2)以200mg/kg浓度给药后,小鼠听力在Click&Toneburst上均可以产生明显变化,同时小鼠的生理状态依然保持良好,因而200mg/kg(庆大霉素)浓度可能是C57BL/6J小鼠药物性致聋的理想剂量。     

Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid

Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound hearing loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitoring the animal's hearing status during the intravenous infusion of EA the technique minimizes the effects of individual variability to the drug regime. Seven cats received a subcutaneous injection of KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing during the infusion. When the ABR thresholds rose rapidly to levels in excess of 90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10–25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong negative correlation (r = − 0.93) between the EA dose and body weight which accounted for much of this variability. Subsequent ABR monitoring showed that this profound hearing loss was both bilateral and permanent. Significantly, blood urea and creatinine levels, monitored for periods of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfunction as indicated by weight loss or oliguria. Cochlear histopathology, examined after a two months to three year survival period, showed an absence of all inner and outer hair cells in the majority of cochleas. The extent of loss of spiral ganglion cells was dependent on their distance from the round window and the period of survival following the deafening procedure. Clearly, the degeneration of spiral ganglion cells continued for several years following the initial insult. Finally, we observed no evidence of renal histopathology. In conclusion, the co-administration of KA and EA produces a profound hearing loss in cats without evidence of renal impairment. Monitoring the animal's hearing status during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this procedure to produce animal models with controlled high frequency hearing losses.     

Efficacy of the cat deafening method: Co-administration of ethacrynic acid and kanamycin

Objective: This study was designed to determine if hearing status monitoring during intravenous infusion of EA reduces individual variability and to evaluate the correlation between EA dose and Bwt.

Materials and methods: Twenty-five cats with the mean age of 24?±?3.7 weeks (range?=?20.6–28.3) and a mean weight of 3.21?±?0.84?kg (range?=?1.9–5.1) were administered a subcutaneous injection of KM (300?mg/kg) followed by an intravenous infusion of EA (1?mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor hearing during the infusion. When ABR thresholds exceeded a 90 dB sound pressure level, the infusion of EA was terminated. Histopathology forapex, middle, and base sections of the cochlea were examined after 6 months.

Results: The dose of EA was optimized for deafening through simultaneous ABR measurements. Bwt was positively correlated with EA dose (mg) (p?R²?=?0.548), which was different from a study previously reported. Cochlear histopathology assessments revealed an absence of organ of Corti in the majority of cochleae.

Conclusion: Co-administration of kanamycin (KM) and ethacrynic acid (EA) was an easy and effective method for deafening procedures in adult animals. Body weight (Bwt) was positively correlated with EA dose (mg) and an optimal EA dose can be calculated.     

Chinchilla models of selective cochlear hair cell loss

Although it is well known that ethacrynic acid (EA) can enhance gentamicin (GM) ototoxicity, there has been no systematic study of the relationship between dosing parameters and inner ear pathology. We examined the effects of two parameters, GM dose and time delay between GM and EA administration, on cochlear and vestibular hair cell loss in chinchillas. 'No delay' groups received one injection of GM (125, 40, 20, or 10 mg/kg i.m.) followed immediately by EA (40 mg/kg i.v.); 'delay' groups received GM (10 mg/kg i.m.) followed by EA 1 or 1.5 h later. Animals were sacrificed 7 days later for evaluation of hair cell loss in the cochlea and vestibular end organs (cristae, saccule and utricle). Vestibular function was assessed prior to sacrifice by measuring the duration of nystagmus induced by cold caloric stimulation. No delay groups had approximately 100% loss of outer hair cells and dose-dependent losses of inner hair cells, ranging from approximately 100% to 58%. In 1 and 1.5 h delay groups, inner hair cell losses were approximately 19% and 0%, outer hair cell losses were approximately 74% and 47%, and outer hair cell loss followed a typical base to apex gradient. Two results were remarkable. First, the three groups with partial inner hair cell loss showed an atypical lesion pattern in which losses were substantially greater in the apical half than in the basal half of the cochlea. Second, there was no vestibular pathology in any group. The results establish dosing parameters that can be used to produce animal models with defined patterns and magnitudes of cochlear hair cell damage, but normal vestibular function and morphology.     

注射用甲泼尼龙琥珀酸钠耳后注射治疗突发性聋

目的　探讨以耳后注射用甲泼尼龙琥珀酸钠作为突发性聋初始激素治疗的效果。方法　72例突发性聋患者随机分为两组,耳后注射组35例（耳）,给予注射用甲 泼尼龙琥珀酸钠20 mg,耳后乳突骨膜下注射,每3 d给药1次;静脉用药组37例（耳）,给予地塞米松磷酸钠注射液10 mg,静脉滴注,每日1次,3 d后减量至5 mg,继续用药3 d后停药。结果　耳后注射组痊愈16耳,显效6耳,有效4耳,无效9耳,总有效率74.3%;全身用药组痊愈17耳,显效5耳,有效4耳,无效11耳,总有效率70.3%。两组差异无统计学意义。结论　耳后注射皮质类固醇激素治疗突发性聋疗效可靠,可作为突发性聋激素治疗的初始给药方法。     

鼓室内注射地塞米松治疗极重度以上突发性聋的临床研究

目的 评估鼓室内注射地塞米松在极重度以上突发性聋仞始治疗中的作用.方法 以发病2周内,未接受任何治疗,初始听力损失(250～4000 Hz均值)>90 dB的突发性聋患者78例作为研究对象,根据患者意愿分为全身激素+局部激素组(22例)、全身激素组(44例)和局部激素组(12例),各组均同时给予扩血管、营养神经的药物治疗和高压氧治疗.全身激素治疗采用地塞米松15 mg/d连用3 d,随后10 mg/d用3 d,最后5 mg/d用3 d.局部激素治疗采用鼓窜内注射5 mg/ml地塞米松0.8 ml,隔日1次,共5次.获取治疗后第10、20、30天的纯音测听结果并进行疗效评估.结果 治疗前影响预后的因素三组间基本匹配.治疗后纯音听阈均值(pure tone average,PTA)改善≥30 dB者所占比例,全身+局部激素组81.82%、局部激素组83.33%、全身激素组88.64%,三组间差异无统计学意义(P=0.726);治疗30 d后PTA改善值分别为:全身+局部激素组41.36 dB、局部激素组43.08 dB、全身激素组51.70 dB,三组间差异无统计学意义(F=1.58,P=0.2133).各组患者治疗后10 d听力改善最为显著,20 d听力基本稳定.纯音测听各频率听阈的改善程度由低频向高频逐渐递减.结论 局部激素治疗作为极重度以上突发性聋的初始治疗与全身激素治疗相比并无优越性.     

Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in ameliorating degeneration after neonatal deafness?

This study examined the combined effects of administration of exogenous GM1 ganglioside and electrical stimulation on the cochlear nucleus (CN) of cats deafened neonatally by ototoxic drugs. Five normal hearing adult cats served as controls. Another 12 cats were deafened bilaterally by daily injections of neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditory brainstem testing demonstrated profound hearing loss. Six of the deaf animals comprised the GM1 group, which received daily injections of GM1 ganglioside (30 mg/kg) for 28-38 days during the period after profound deafness was confirmed, and prior to receiving a cochlear implant. The non-GM1 group (n=6) received no treatment during this interim period. All the deafened animals underwent unilateral cochlear implantation at 6-9 weeks postnatal and received several months (mean duration, 32 weeks) of chronic electrical stimulation (4 h/day, 5 days/week). Stimulation was delivered by intracochlear bipolar electrodes, using electrical signals that were designed to be temporally challenging to the central auditory system. Results showed that in the neonatally deafened animals, both the GM1 and non-GM1 groups, the volume of the CN was markedly reduced (to 76% of normal), but there was no difference between the animals that received GM1 and those that did not. The cross sectional areas of spherical cell somata in both GM1 and non-GM1 groups also showed a highly significant reduction in size, to < or =75% of normal after neonatal deafening. Moreover, in both the GM1 and non-GM1 groups, the spherical cells in the CN ipsilateral to the implanted cochlea were significantly larger (6%) than cells in the control, unstimulated CN. Again, however, there was no significant difference between the GM1 group and the non-GM1 group in spherical cell size. These results contrast sharply with previous reports that exogenous GM1 prevents CN degeneration after neonatal conductive hearing loss and partially prevents spiral ganglion cell degeneration when administered immediately after ototoxic drug deafening in adult animals. Taken together, findings to date suggest that GM1 may be effective in preventing degeneration only if the GM1 is administered immediately at the time hearing loss occurs.     

cis-diamminedichloroplatinum cochlear toxicity

Twenty-nine guinea pigs were divided into three groups. The first group received distilled water 2 ml/kg ip daily; the second group received DDP 2 mg/kg ip daily; and the third group DDP 4 mg/kg ip daily. ABR hearing threshold was tested before injection. Twenty-four hours after systemic administration, ABR hearing threshold was tested again. The animals were killed and the cochlear specimens were observed under light, scanning and transmission electron microscopes. No abnormality regarding ABR hearing threshold and cochlear morphology was observed in the first group. In the second group, ABR hearing threshold was elevated, inner and outer hair cells, supporting cells, striae vascularis and spiral ganglions were damaged. In the third group, ABR hearing threshold elevated markedly. All above-mentioned cells were severely damaged. The experiment showed that the cochlear damage induced by DDP was dose related. The severest damage was seen in the second turn of the cochlea. The damage to the Deiters' cells was earliest and severest. The outer hair cells were more vulnerable to the damage than the inner hair cells did.     

Electric-acoustic stimulation of the auditory system. New technology for severe hearing loss.

Various devices have been developed to overcome the widespread phenomenon of different degrees of hearing deficits between mild and profound hearing loss. Basically, we differentiate between acoustic stimulation (hearing aids), restricted to cases with a partially functioning cochlear receptor, and electrical stimulation (cochlear implants), stimulating the auditory nerve directly in cases with profound or total hearing loss. For the first time, animal data have been collected that indicate the possibility of nearly interference-free use of both stimulation types simultaneously. In addition, we have gathered the first clinical patient experience, which confirms the encouraging results. Future implications for patients with severe high-frequency hearing loss are discussed.     

Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss

Increase in spontaneous neural activity after noise-induced hearing loss has frequently been associated with the phenomenon of tinnitus. Eighteen juvenile and adult cats were exposed for 2 h to a 6 kHz tone with an intensity of 115 dB SPL at the cat’s head. Seven non-exposed littermates and seven other normal hearing cats were used as age-matched controls. The trauma cats showed localized hearing losses, as assessed by ABR, ranging from less than 20 to 60 dB. The frequency representation in primary auditory cortex was mapped using an eight-electrode array. Single-unit spontaneous activity was recorded for 15 min. Peak cross-correlation coefficients (R) for unit cluster activity recorded on separate electrodes were calculated. We found elevated spontaneous firing rates in regions with reorganization of the tonotopic map compared to the neurons in the non-reorganized cortical regions in the same animals. A second finding was that in these regions the peak cross-correlation coefficients were also increased relative to the non-reorganized parts. A third finding was that exposed animals showed higher spontaneous activity compared to controls regardless of the presence of cortical reorganization. This may be a correlate of tinnitus in the presence of only minor hearing losses.     

卡那霉素和速尿联合用药后豚鼠耳蜗听功能研究

目的 探讨卡那霉素和速尿联合用药对豚鼠耳蜗听功能的影响。方法实验组50只豚鼠肌肉注射卡那霉素500mg／kg，同时静脉注射速尿40mg／kg，空白对照组4只豚鼠。于药物注射3天（25只）和7天（25只）后行听觉脑干诱发电位（auditory brainstem response，ABR）．听神经复合动作电位（compound action potential，CAP）及耳蜗微音电位（cochlear microphonic，CM）检测，观察所有动物的中耳结构，对实验组和对照组豚鼠耳蜗听功能进行统计学分析。结果观察所有实验组豚鼠的中耳结构可见鼓膜完整．无充血或者穿孔．听骨链完整．听骨结构无破坏或者移位。豚鼠用药后听阈的个体差异较大，用药后同一频率CAP阈值低于ABR阈值，有的豚鼠用药后CAP阈值轻度提高，但是CM明显异常；将听阈〉95 dB SPL的豚鼠分为用药3天组和用药7天组，发现用药3天组各频率（2kHz，4kHz，8kHz和16kHz）比正常对照组同一频率的听力阈值明显提高（方差分析P〈0．01，差异有显著性），而用药3天组和用药7天组各频率（2kHz，4kHz，8kHz和16kHz）比较阈值没有差别（方差分析P〉0．05，差异没有显著性），用药后较高频率（8kHz，16kHz）的听力损失大于较低频率（2kHz，4kHz）。结论卡那霉素和速尿联合用药后3天可使豚鼠听功能严重受损，因此，卡那霉素和速尿联合用药是建立耳聋模型的一种快速而有效的方法。