脉冲噪声暴露后大鼠听皮层神经颗粒素的表达研究

目的揭示脉冲噪声暴露后不同时期大鼠听皮层神经颗粒素(neurogranin,Ng)表达的变化。方法将50只成年SD大鼠随机分为5组:正常对照组及脉冲噪声暴露后3、7、14、28天组,每组10只。脉冲噪声暴露条件为:平均压力峰值156dB SPL,脉宽为0.25ms,暴露50次,每次间隔6s。于噪声暴露前及噪声暴露后即刻、3、7、14、28天检测各组大鼠ABR反应阈,同时,应用Western blot方法检测各组大鼠听皮层中的Ng的含量。结果与对照组相比,各组大鼠噪声暴露后即刻、3、7、14、28天各频率ABR反应阈均明显提高(P<0.05),噪声暴露后第7天,各频率ABR阈值有所恢复,第14天时趋于稳定;与对照组(0.68±0.08)比较,噪声暴露后第3、7、14天组大鼠听皮层中Ng的含量分别为0.96±0.05、1.11±0.05、0.78±0.04,显著高于对照组,第28天组为0.36±0.03,显著低于对照组,差异均有统计学意义(P<0.05)。结论噪声暴露后,大鼠ABR反应阈明显升高,听皮层Ng的表达呈现一个先上升后降低的过程,提示脉冲噪声刺激对大鼠听觉系统产生了一定持续性的影响,听皮层出现突触可塑性变化。     

噪声暴露下大鼠行为学和海马促肾上腺皮质激素释放因子蛋白表达的改变

目的观察噪声暴露下大鼠行为学的改变,探讨噪声对生物体情绪行为和听力的负性影响及其可能的发生机制。方法选取行为学指标和ABR反应阈接近的健康大鼠24只,随机分为3组,每组8只。对照组(A组):正常喂养;噪声组(B组):每天固定时间噪声暴露4 h,持续28 d;氟西汀组(C组):噪声暴露的条件和时间与噪声组相同,每天噪声暴露后即腹腔注射剂量为10 mg/kg的氟西汀,持续28 d,噪声暴露前1 d、第7、14、28 d观察大鼠的旷场行为并检测ABR反应阈,实验前后记录大鼠的糖水偏爱百分比,最后断头取脑,剥离大鼠海马,Western-blot法测定各组大鼠海马CRF表达。结果第7、14、28 d,与对照组比较,其它组大鼠的旷场行为表现显著改变,差异有统计学意义(P<0.01);氟西汀组大鼠与噪声组比较,旷场行为差异均有统计学意义(P<0.01)。噪声暴露28d后,与对照组相较,噪声组和氟西汀组糖水偏爱百分比明显下降,差异有统计学意义(P<0.05);与噪声组比较,氟西汀组大鼠糖水偏爱明显增加,差异有统计学意义(P<0.05)。随着噪声暴露时间的延长,其ABR反应阈升高,差异有明显统计学意义(P<0.01)。氟西汀组海马CRF的表达较正常组增加,但较噪声组表达降低,各组间差异均有统计学意义(P<0.05)。结论长期的噪声暴露可使大鼠产生焦虑抑郁样行为,抗抑郁剂能改善这些行为的改变。海马CRF表达的增加可能参与噪声应激所致的大鼠行为学变化。     

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。     

脉冲噪声暴露后大鼠频率特异性听性脑干反应变化特点及意义

目的探讨脉冲噪声暴露后不同时间大鼠频率特异性听性脑干反应变化特点及意义。方法成年SD大鼠50只分为5组:正常组及脉冲噪声暴露后3、7、14、28天组,每组10只。脉冲噪声条件为:平均压力峰值为156dBSPL,脉宽0.25ms,暴露50次,分别于暴露前后对大鼠行ABR检测,刺激声为短音(tonepip),频率范围为2～32kHz。结果①正常大鼠2、4、8、16、32kHz的平均听阈分别为68.5±2.67、58.2±2.58、39.3±3.33、37.5±2.95、37.3±3.60dBSPL;②与脉冲噪声暴露前相比较,暴露后各组2、4、8、16、32kHzABR阈值均明显提高,差异有统计学意义(P<0.05),其中高频阈移的幅度较低频阈移幅度大;在暴露后恢复第7天时,各频率ABR阈值有所恢复,第14天时恢复明显,第28天时与第14天接近。结论脉冲噪声暴露后大鼠频率特异性听性脑干反应阈值升高,第7天后开始有所恢复,可为后期进一步研究听觉中枢可塑性建立稳定有效的急性声损伤动物模型。     

噪声对大鼠耳蜗基底膜凋亡诱导因子表达的影响

目的探讨噪声暴露前后凋亡诱导因子（AIF）在大鼠不同回基底膜外毛细胞的表达差异以及与噪声性聋高频听力易损性的关系。方法40只SD大鼠随机分为正常对照组和噪声暴露组：噪声暴露组给予声强为115dB SPL白噪声暴露,每天2小时,连续3天,对照组不予噪声暴露。分别于噪声暴露前1日、暴露后1、3、7、14日对两组大鼠行ABR检测,最后一次ABR检测后对两组大鼠耳蜗基底膜行鬼笔环肽—异硫氰酸荧光素(Phalloidin-FITC)染色。West-ern blot和免疫荧光染色法观察两组大鼠耳蜗不同回基底膜处AIF的表达。结果大鼠噪声暴露后与暴露前相比,ABR各频反应阈值于暴露后1天最高,随时间逐渐恢复,14天时趋于稳定,听力低频阈移约10dB,高频阈移有30dB (P<0.05);基底膜铺片FITC染色示噪声暴露组底回基底膜毛细胞较顶回缺失严重,且有纤毛排列紊乱并出现融合,而对照组毛细胞排列整齐,纤毛呈V或W型,两组间外毛细胞计数比较差异有统计学意义(P<0.05);Western blot结果示,在正常情况下,顶回基底膜的AIF表达高于底回,噪声暴露后,AIF顶、底回基底膜表达均较对照组相应部位增高,且顶回较底回更为显著(P<0.05)。结论噪声暴露过程中,AIF在促凋亡的同时更发挥出了氧化还原酶的作用,因而AIF在耳蜗基底膜顶、底回的表达差异,可能是噪声性聋高频听力易损性的分子机制之一。     

强脉冲噪声暴露后大鼠听皮层蛋白质差异表达的研究

目的 运用蛋白质组学技术检测强脉冲噪声暴露后不同时间点大鼠听皮层蛋白质表达谱的差异.方法 健康成年SD大鼠分为三组:正常对照组、急性脉冲噪声暴露组及噪声暴露后恢复组.脉冲噪声平均压力峰值(声压级)为156 dB,脉宽为0.25 ms,暴露50次.听性脑干反应(ABR)评价大鼠听功能;运用二维凝胶电泳+质谱分析法对各组大鼠听皮层蛋白质表达谱进行检测,比较其差异,并对表达变化较大的蛋白进行质谱鉴定.结果 与对照组相比,急性暴露组及恢复组在ABR各频率(2、4、8、16、32 kHz)阈值均明显提高(P值均＜0.05);噪声暴露即刻,ABR各频率听阈均有40 ～60 dB的上升;暴露后第7天,各频率ABR阈值有所恢复,第14天时趋于稳定.噪声暴露前后听皮层组织中的差异蛋白有64个,选取变化倍数大的50个点进行酶切质谱鉴定.其中有14个点不可信,剩余36个点所代表的27种蛋白被鉴定出来.所鉴定的差异蛋白主要包括:细胞骨架相关蛋白,线粒体及能量代谢相关蛋白,与突触重塑、神经递质释放及神经元兴奋性相关的蛋白等.结论 强脉冲噪声暴露可引起大鼠听皮层中多种蛋白质表达的变化,这些差异蛋白可能参与强噪声听力损伤的修复过程,以及听觉中枢的可塑性变化及功能重组.     

噪声暴露对大鼠耳蜗碳酸酐酶活性及mRNA表达的影响

目的：探讨噪声暴露后耳蜗碳酸酐酶（CA）活性及其mRNA表达的变化。方法：选用健康白色大鼠24只,随机分为4组,1组为正常对照组,另外3组为实验组。实验组暴露在4kHz、110dBSPL窄带白噪声环境中4h／d,分别测试噪声暴露1d、1周、3周和对照组大鼠脑干反应（ABR）。采用免疫组织化学法观察耳蜗外侧壁CA的活性,RT-PCR检测大鼠耳蜗CAIImRNA的表达。结果：噪声暴露后大鼠ABR阈值较对照组显著增加;而耳CA活性及CAIImRNA的表达较对照组显著下降;随着噪声暴露时间的延长,ABR阈值增加而cA活性及CAIImRNA的表达呈下降趋势。结论：噪声刺激能降低耳蜗CA的活性及CAIImRNA的表达,CA可能参与了噪声性聋的发病机制。     

模拟中长期微重力和噪声环境对大鼠听功能及内耳毛细胞凋亡的影响

目的 研究模拟中长期微重力和噪声环境对大鼠听功能及内耳细胞凋亡的影响.方法 36只SD大鼠随机分为两组:空白组(6只)和实验组(30只).实验组给予持续尾部悬吊模拟微重力及飞船舱内噪声(稳态噪声+脉冲噪声)暴露,分别于悬吊及暴露前、悬吊及暴露3天、1周、2周、4周和8周后检测双耳ABR反应阈,并于悬吊及暴露3天、1周、2周、4周和8周取实验动物耳蜗行免疫组化染色观察半胱氨酸天冬氨酸蛋白酶3(caspase-3)在内耳的表达.空白组不做任何处理,常规饲养,于实验前及实验3天、1周、2周、4周和8周分别检测双耳ABR反应阈,并于饲养8周后取耳蜗行免疫组化染色观察.结果 实验前两组大鼠ABR反应阈差异无统计学意义(P＞0.05).实验组大鼠悬吊及噪声暴露后各时间点ABR反应阈较空白组均明显增高(P＜0.01),悬吊及暴露4周实验组大鼠ABR反应阈为90.00±4.26 dB SPL,明显高于3天、1周、2周及8周时(P＜0.05);悬吊及暴露8周大鼠ABR反应阈(80.00±5.22 dB SPL)有所下降,与暴露2周(85.00±4.77 dB SPL)、4周大鼠比较差异有统计学意义(P＜0.01).悬吊及噪声暴露后大鼠内耳细胞caspase-3的表达较空白组明显增强,且在一定时间内随暴露时间的延长其表达有逐渐增强的趋势,尤以悬吊及暴露4周时最明显,暴露8周时其表达强度较4周时明显下降.结论 模拟中长期微重力和噪声环境对大鼠的听功能有明显损伤,且与内耳细胞凋亡呈相同的趋势;微重力和噪声因素造成的听功能损伤可能与内耳细胞的凋亡有关.     

长期注射水杨酸钠对大鼠下丘GAD67和GABAAα1、c-fos表达的影响

目的 通过观察长期注射水杨酸钠对大鼠听性脑干反应(ABR)及下丘GAD67和GABAAα1、c-fos表达的影响,探讨大鼠下丘GAD67、GABAAα1、c-fos表达的改变在水杨酸钠耳毒性中的可能机制。 方法 将24只成年健康Wistar大鼠随机分为2组:水杨酸钠组(肌肉注射10%水杨酸钠175 mg/kg,2次/d,连续28 d)、对照组(每天相同时间注射等量生理盐水,连续28 d)。两组大鼠在处死前进行ABR检测并观察ABR反应阈及波Ⅲ潜伏期的变化,然后将大鼠断头处死并迅速剥离下丘,采用实时荧光定量PCR(real-time PCR)、蛋白质印迹(Western blot)方法检测下丘GAD67、GABAAα1、c-fos mRNA及蛋白表达的变化。 结果 ①药物注射28 d后,水杨酸钠组较注射前以及对照组ABR反应阈明显升高,波Ⅲ潜伏期明显延长,差异有统计学意义(P<0.01);②水杨酸钠组GAD67、GABAAα1、c-fos mRNA及其蛋白表达水平较对照组明显升高,差异有统计学意义(P<0.01)。 结论 GAD67、GABAAα1、c-fos均不同程度参与了水杨酸钠耳毒性的发生发展过程, c-fos表达的上调则可能与水杨酸钠作用于机体后引起听觉中枢神经活动增强有关。     

西地那非对豚鼠噪声性听觉损伤阈移的影响

目的 探讨西地那非(sildenafil)对豚鼠噪声性听觉损伤阈移的影响.方法 将豚鼠按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10只.西地那非组及噪声组豚鼠在白噪声(A计权声压级110 dB)暴露1周后分别腹腔注射西地那非10 mg/(kg·d)及生理盐水4mL/(kg·d),连续给药4周.分别测试噪声暴露前1日、噪声暴露后1、2及4周听性脑干反应(ABR)阈值,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 噪声暴露1后,噪声暴露组豚鼠ABR阈值(声压级)平均提高19.1 dB,随着时间推移,阈移逐渐加大,暴露后4周,阈值平均提高22.0 dB;西地那非组噪声暴露后ABR阈值提高19.8 dB,给药后阈移逐渐减小,给药后4周,阈值仅平均提高4.8 dB.西地那非组与噪声暴露组相比,除噪声暴露结束后这一时间点以外,其余给药后各时间点ABR阈值差异均具有统计学意义(P值均＜0.05).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.     

模拟失重和噪声对大鼠听功能及耳蜗Corti 器损伤的协同作用

目的：探讨模拟失重和噪声对大鼠听功能及耳蜗Corti器损伤的协同作用。方法48只大鼠随机分为空白组、失重组、噪声组和失重＋噪声组,每组12只。失重组以Morey －Holton法模拟失重环境,噪声组暴露的噪声环境为模拟航天载人飞船内复合噪声,包括72±2 dB SPL的持续稳态噪声和160 dB SPL的脉冲噪声,失重＋噪声组则同时暴露于上述失重及噪声环境中,空白组常规饲养,不做任何处理。分别于暴露1周和2周后,每组随机选出6只大鼠行ABR阈值检测后取材行 HE染色、免疫荧光（DAPI）染色及扫描电镜观察耳蜗的形态学变化。结果暴露2周后大鼠ABR阈值较暴露1周时升高,失重＋噪声组ABR阈值最高（ P＜0．01）,其次为噪声组。HE染色示暴露1周和2周后除空白组外各组大鼠耳蜗Corti器均有不同程度的损伤,失重＋噪声组最严重。免疫荧光染色示暴露1周后大鼠耳蜗毛细胞死亡方式以肿胀坏死为主,失重＋噪声组最严重（肿胀率10％）,其次为噪声组（肿胀率3．33％）;暴露2周后大鼠耳蜗外毛细胞以核缺失为主,失重＋噪声组缺失率最高（缺失率13．6％）,其次为噪声组（缺失率12．7％）,失重组毛细胞缺失以内毛细胞为主。扫描电镜示,失重＋噪声组毛细胞静纤毛损伤最严重,其次为噪声组,再次为失重组。结论模拟失重和噪声环境对大鼠听功能的影响有协同作用,且这种协同作用对耳蜗Corti器有显著的损伤作用。     

Prevention of impulse noise-induced hearing loss with antioxidants

CONCLUSION: These findings indicate a strong protective effect of ALCAR and NAC on impulse noise-induced cochlear damage, and suggest the feasibility of using clinically available antioxidant compounds to protect the ear from acute acoustic injury. OBJECTIVE: Reactive oxygen species have been shown to play a significant role in noise-induced hearing loss. In the current study, the protective effects of two antioxidants, acetyl-L-carnitine (ALCAR) and N-L-acetylcysteine (NAC), were investigated in a chinchilla model of hearing loss resulting from impulse noise. It was hypothesized that pre- and post-treatment with these antioxidants would ameliorate the effects of impulse noise compared to saline-treated controls. MATERIAL AND METHODS: Eighteen animals were randomly assigned to 1 of 3 groups and exposed to impulse noise at a level of 155 dB peak SPL for 150 repetitions. ALCAR or NAC were administered twice daily (b.i.d.) for 2 days and 1 h prior to and 1 h following noise exposure, and then b.i.d. for the following 2 days. For the control group, saline was injected at the same time points. Auditory brainstem responses (ABRs) were recorded. Cochlear surface preparations were made to obtain cytocochleograms. RESULTS: Three weeks after exposure, permanent threshold shifts for the experimental groups were significantly reduced to approximately = 10-30 dB less than that for the control group (p < 0.01). Less hair cell loss was also observed in the ALCAR and NAC groups than in the control group.     

Hypoxic changes in the central nervous system of noise-exposed mice

CONCLUSION: After a noise-induced transient threshold shift, hypoxia occurred in the central nervous system, especially in the auditory cortex, the hippocampus, and the inferior colliculus. OBJECTIVES: Noise-induced inner ear hypoxia was shown by measurement of an increase in hypoxia-inducible factor-1 alpha, which is expressed? in the nucleus under hypoxic conditions. This study uses pimonidazole to localize site-specific hypoxic changes occurring in the mouse central auditory pathway during noise-induced auditory threshold shift. METHOD: BALB/c hybrid mice with normal hearing were exposed to 122 dB SPL white noise for 3 h. Immediately after exposure to the noise, and 7 d after noise exposure, the brains of mice were collected. Brains were cryosectioned into slices 15 microm thick and examined by immunofluorescence after staining with pimonidazole HCl. RESULTS: After 3 h of exposure to 120 dB SPL noise, the hearing thresholds of mice decreased to 51.1+/-8.6 dB SPL (n =14), but hearing recovered in 7 d. After noise exposure, pimonidazole signal increased in the auditory cortex, the hippocampus, and the inferior colliculus. The pimonidazole signal remained elevated after 7 d. In control mice, pimonidazole did not stain any brain region.     

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。     

Prevention of impulse noise-induced hearing loss with antioxidants

Conclusion These findings indicate a strong protective effect of ALCAR and NAC on impulse noise-induced cochlear damage, and suggest the feasibility of using clinically available antioxidant compounds to protect the ear from acute acoustic injury. Objective Reactive oxygen species have been shown to play a significant role in noise-induced hearing loss. In the current study, the protective effects of two antioxidants, acetyl-L-carnitine (ALCAR) and N-L-acetylcysteine (NAC), were investigated in a chinchilla model of hearing loss resulting from impulse noise. It was hypothesized that pre- and post-treatment with these antioxidants would ameliorate the effects of impulse noise compared to saline-treated controls. Material and methods Eighteen animals were randomly assigned to 1 of 3 groups and exposed to impulse noise at a level of 155 dB peak SPL for 150 repetitions. ALCAR or NAC were administered twice daily (b.i.d.) for 2 days and 1 h prior to and 1 h following noise exposure, and then b.i.d. for the following 2 days. For the control group, saline was injected at the same time points. Auditory brainstem responses (ABRs) were recorded. Cochlear surface preparations were made to obtain cytocochleograms. Results Three weeks after exposure, permanent threshold shifts for the experimental groups were significantly reduced to ≈10–30 dB less than that for the control group (p<0.01). Less hair cell loss was also observed in the ALCAR and NAC groups than in the control group.     

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.     

长期注射水杨酸钠大鼠下丘EphA4的表达

目的：通过观察长期水杨酸钠作用后大鼠ABR及下丘EphA4mRNA表达变化,探讨下丘EphA4表达在水杨酸钠耳毒性中的作用。方法将30只健康成年雄性SD大鼠随机分为5组,每组6只：正常对照组（不予任何处理）,肌注7天组（肌肉注射水杨酸钠175 mg／kg,每天2次,间隔8小时,连续7天）,肌注14天组（水杨酸钠用法同前,持续14天）,恢复14天组（肌注水杨酸钠14天后,停药恢复14天）,恢复28天组（肌注水杨酸钠14天后,停药恢复28天）。对各组大鼠分别于相应时间点进行 ABR 检测后处死并迅速分离下丘,采用实时荧光定量PCR（real－time PCR）的方法检测各组大鼠下丘中EphA4mRNA表达。结果①肌注7、14天组大鼠的ABR反应阈分别为38．33±3．73、44．16±1．86 dB SPL,较对照组（30．83±1．86 dB SPL）明显升高（P＜0．05）;恢复28天组大鼠的ABR反应阈（32．50±2．50 dB SPL）与对照组（30．83±1．86 dB SPL）相比,差异无明显统计学意义（P＞0．05）;②肌注7天组和恢复14天组大鼠下丘 EphA4mRNA 表达（分别为：0．69±0．11、0．67±0．09）均低于对照组大鼠（0．99±0．01）（均为P＜0．05）;恢复28天组大鼠下丘EphA4mRNA表达（0．88±0．04）与对照组大鼠比较差异无统计学意义（P＞0．05）。结论长期注射水杨酸钠后大鼠下丘的 EphA4表达呈可逆性下降,且与水杨酸钠注射后大鼠听功能损伤的变化一致,推测下丘神经元轴突中EphA4参与了水杨酸钠耳毒性的机制。