成纤维细胞生长因子耳蜗内灌注防治爆震性聋的实验研究

选用豚鼠１９只，震前于圆窗龛放银球电极测复合动作电位（ＣＡＰ）反应阈，爆震后测ＣＡＰ，于耳蜗底回打孔，分别灌注酸性成纤维细胞生长因子（ａＦＧＦ）和碱性成纤维细胞生长因子（ｂＦＧＦ），４８小时后再测ＣＡＰ，处死动物做耳蜗琥珀酸脱氢酶（ＳＤＨ）组化染色铺片。结果爆震后灌注ｂＦＧＦ、ａＦＧＦ两组动物４８小时ＣＡＰ平均阈值分别为８８．７ｄＢ和９３．２ｄＢ，而单纯打孔组和灌注外淋巴组ＣＡＰ平均阈值分别为１１９．４ｄＢ和１０７．５ｄＢ，差异有显著性（Ｐ＜０．０５和０．０１）。铺片结果示灌流生长因子两组动物耳蜗毛细胞损伤程度比其他两组要轻。结果提示ｂＦＧＦ、ａＦＧＦ耳蜗内灌注对爆震性聋ＣＡＰ反应阈恢复有促进作用，在耳蜗声损伤过程中有保护和修复功用。     

碱性成纤维细胞生长因子肌肉注射防治爆震性聋的实验观察

目的 为验证碱性成纤维细胞生长因子（ｂＦＧＦ）对爆震性耳聋 防治作用。方法 选用２豚鼠３５只，分为４组：ｂＦＧＦ肌注治疗组（１０只），震后即刻给予ｂＦＧＦ肌注（５０ＩＵ／１００ｇ）连用４周，生理盐水肌注治疗组（１０只），疗程同前；ｂＦＧＦ肌注预防组（１０只），生理盐水肌注预防组（５只），剂量同治疗组连用２周。动物爆震１００发，每秒１发，脉宽０．５ｍｓ，压力峰值１７２．０ｄＢＳＰＬ，爆震前后测定ＡＢ     

雏鸡庆大霉素致聋后的听力恢复及表皮生长因子对其恢复的影响

为了探讨庆大霉素（ＧＭ）致聋雏鸡的听力恢复和表皮生长因子（ＥＧＦ）对其听力的影响，将１周龄雏鸡随机分成正常对照组、ＧＭ组和ＥＧＦ组。ＧＭ组雏鸡注射ＧＭ１０ｄ，每天１００ｍｇ／ｋｇ，ＥＧＦ组注射ＧＭ１０ｄ后再注射表皮生长因子（ＥＧＦ）５ｄ，每天１００μｇ／ｋｇ，分别观察ＡＢＲ阈值的变化。结果发现：ＧＭ组停药当天雏鸡ＡＢＲ阈值明显升高（Ｐ＜０．０１），停药后ＡＢＲ阈值逐渐恢复，但２１ｄ仍未恢复正常；ＥＧＦ组停药后与同期ＧＭ组雏鸡比较，ＡＢＲ阈值明显下降。结果提示，ＧＭ致聋雏鸡听力可以恢复，ＥＧＦ可明显促进雏鸡听觉功能恢复。     

爆震时冲击波对豚鼠前庭功能影响的实验观察

应用ＢＳＴ－Ⅱ型生物激波管作为爆震源，对１７只健康成年豚鼠进行了冲击波实验。眼震电图（ＥＮＧ）观察记录其爆震前和爆震后即刻以及爆震后４８ｈ的前庭功能变化。观察指标为慢相角速度（ＳＶ）、频率（Ｆ）、幅度（Ａ）和持续时间（Ｄ）。实验结果发现：爆震产和爆震后即刻以及爆震后４８ｈ左右耳ＥＮＧ的ＳＶ、Ａ、Ｄ的变化差异有高度显著性（Ｐ〈０．０１），Ｆ的变化也有显著性差异（Ｐ〈０．０５），结果显示爆震时冲击波具     

鸡内耳听觉器官的原代培养

为在体外环境中的毛细胞形态学观察及其相关研究提供组织模型，应用原代器官培养技术，对出生后８～１６ｄ的２０只鸡的听觉上皮——基底乳头（ＢＰ）连续培养１～７ｄ，观察并比较了ＢＰ组织中的细胞存活状态。结果显示，培养期内ＢＰ组织构型与毛细胞、支持细胞形态在离体条件下仍能良好维持，与在体对照组无显著差别。以重组碱基成纤维细胞生长因子（ｂＦＧＦ）－胶原复合物为基质的贴壁培养法效果理想，培养６ｄ之内ＢＰ存活良好；悬浮培养法适用于４８ｈ的短期培养。     

内耳色素与爆震性听损伤

目的 探讨内耳色素与爆震性听损伤的关系。方法 选用豚鼠４８只，分为：白化豚鼠爆震组，杂色豚鼠爆震组，正常对照组。爆震前及爆震后６小时、１、２、７、１４、２１天测定Ａ、Ｂ组豚鼠ＡＢＲ阈值。处死豚鼠做耳蜗铺片、耳蜗树脂包埋半薄切片、耳蜗扫描电镜制样，观察耳蜗内色素及耳蜗损伤情况。结果 光镜下杂色豚鼠可见耳蜗内色素颗粒，而白化豚鼠未见。爆震后白化豚鼠听力损伤比杂色豚鼠严重，其听力恢复亦较杂色豚鼠慢。爆震     

聚DL-天冬氨酸对庆大霉素耳毒性拮抗作用的实验研究

目的　研究聚ＤＬ天冬氨酸（ｐｏｌｙ ＤＬａｓｐａｒｔｉｃ ａｃｉｄ,ＰＡＡ） 对Ｆ３４４ 大鼠庆大霉素（ｇｅｎｔａｍｉｃｉｎ,ＧＭ） 耳毒性的拮抗作用。方法　选用健康Ｆ３４４ 大鼠５０ 只,随机分４ 组：Ⅰ为ＧＭ、Ⅱ为ＰＡＡ＋ ＧＭ、Ⅲ为ＰＡＡ、Ⅳ为生理盐水对照组;通过观测４ 组大鼠不同时期、不同频率听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓ,ＡＢＲ）阈值的改变;计数耳蜗毛细胞死亡率,以观察ＰＡＡ对Ｆ３４４ 大鼠ＧＭ 耳蜗毒性的拮抗作用;用双向扩散血清培养基检测法观察ＰＡＡ 对ＧＭ 抗菌活性的影响。结果　Ⅰ组短纯音１０ ｋＨｚ、８ ｋＨｚ ＡＢＲ阈值与其他３ 组差异有显著性（ Ｐ＜ ０．０１） ,给药１８ ｄ 耳蜗毛细胞死亡率与其他３ 组间差异也有显著性（ Ｐ＜０ ．０１）。结论　ＰＡＡ对庆大霉素的耳毒性具有拮抗作用,且不减低其抗菌活性。     

压力波对豚鼠耳蜗外侧壁微循环及听阈的影响

本研究应用生物微球技术、ＨＲＰ示踪显色法，结合光学显微镜，分别将对照组及爆震后２、６、２４ｈ组豚鼠耳蜗外侧壁血流量、微血管数量进行测量，并测试听性脑子反应。结果：爆震前、后各组ＡＢＲ平均阈值，组间差异显著（Ｐ＝０．０００４），６ｈ组阈移最大，其次为２４ｈ组，２ｈ组最小。爆震后豚鼠耳蜗侧壁血流量，无显著差异（Ｐ＞０．０５），而各回血流量有波动；爆震后耳蜗外侧壁血流量与阈移呈负相关（ｒ＝－０．５９３，Ｐ＜０．０５），外侧壁微血管的数量，因时间而变化，与血流量变化相吻合。讨论了爆震后耳蜗外侧壁血流量变化与听力损失、外侧微血管数量变化之间的关系。     

冲击波对豚鼠螺旋神经节细胞谷氨酸免疫反应及听阈的影响

豚鼠经平均压力峰值１８４ｄＢ（ＳＰＬ）的冲击波一次暴露后，分别测８、２４、７２小时、７天的螺旋神经节（ＳＧ）细胞谷氨酸免疫反应（Ｇｌｕ－ＩＲ）阳性产物的光密度值，均较对照组明显增高（Ｐ＜０．０１）。以８小时者光密度最大，７天者最小。免疫透射电镜发现，爆震后８小时豚鼠ＳＧⅠ型、Ⅱ型细胞浆内ＬＵ－ＩＲ阳性产物明显增多。不同时间组ＡＢＲ阈移与Ｇｌｕ－ＩＲ阳性产物光密度的变化率成正相关（ｒ＝０．９１９，Ｐ＜０．０５）。提示冲击波所致听力损伤与ＳＧ细胞内Ｇｌｕ变化有关。     

鸡内耳听觉器官的原代培养

为在体外环境中的毛细胞形态学观察及其相关研究提供组织模型，应用原代器官培养技术，对出生后８－１６ｄ的２０只鸡的听觉上皮－基底乳头（ＢＰ）连续培养１－７ｄ，观察并比较了ＢＰ组织中的细胞存活状态。结果显示，培养期内ＢＰ组织构型与毛细胞、支持细胞形态在离体条件下仍能良好维持，与在体对照组无显著差别。以重组碱基成纤维细胞生长因子（ｂＦＧＦ）－胶原复合物为基质的贴壁培养法效果理想，培养６ｄ之内ＢＰ存活良好；     

Protective Effect of Basic Fibroblast Growth Factor on Auditory Hair Cells after Noise Exposure

The purpose of this study was to observe the protective effects of basic fibroblast growth factor (bFGF) on the cells of the inner ear using in vivo experiments. The studies were carried out using guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea. The compound action potential (CAP) was measured before and after exposure to a sound simulating an explosion. The difference in CAP was significant between the bFGF-perfused group and the control group ( p <0.01, t = 3.896) and between the bFGF-perfused group and the artificial perilymph-perfused group ( p <0.05, t = 2.520). The cochleae were removed and hair cell loss estimated from surface preparations. Acoustic trauma caused loss of outer hair cells in the first and second turns of the cochlea in the bFGF-perfused group and the artificial perilymph-perfused group and partial loss of inner hair cells in the control group. Treatment with bFGF reduced the loss of inner hair cells compared to that of control animals. Our results demonstrate that treatment with bFGF protects the hair cells from acoustic trauma and may facilitate the recovery of hearing.     

Protective effect of basic fibroblast growth factor on auditory hair cells after noise exposure

The purpose of this study was to observe the protective effects of basic fibroblast growth factor (bFGF) on the cells of the inner ear using in vivo experiments. The studies were carried out using guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea. The compound action potential (CAP) was measured before and after exposure to a sound simulating an explosion. The difference in CAP was significant between the bFGF-perfused group and the control group (p < 0.01, t = 3.896) and between the bFGF-perfused group and the artificial perilymph-perfused group (p < 0.05, t = 2.520). The cochleae were removed and hair cell loss estimated from surface preparations. Acoustic trauma caused loss of outer hair cells in the first and second turns of the cochlea in the bFGF-perfused group and the artificial perilymph-perfused group and partial loss of inner hair cells in the control group. Treatment with bFGF reduced the loss of inner hair cells compared to that of control animals. Our results demonstrate that treatment with bFGF protects the hair cells from acoustic trauma and may facilitate the recovery of hearing.     

Basic flbroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment II, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was     

Basic fibroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

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Nitric oxide in glutamate-induced compound action potential threshold shifts

OBJECTIVE: Investigate the role of NO as a neurotransmitter in the gerbil cochlea and the effects of (7-NI) on compound action potential (CAP) threshold elevations induced by l-glutamate, an agonist at the NMDA glutamate receptor subtype, to further elucidate the role of NO in cochlear excitotoxicity. METHOD: In anesthetized gerbils, CAP thresholds were recorded before and after cochlear perfusions with a control solution of artificial perilymph (APS) and a test solution of L-glutamate (GA) in three experimental groups. RESULTS: The control group showed no CAP threshold elevations (p<0.05) when APS was perfused after systemic pre-treatment with 7-NI. GA perfusion alone caused significant elevation (p<0.05) of the mean cochlear CAP threshold (25 dB SPL+/-5.8 dB to 78 dB SPL+/-19.5 dB). The CAP threshold elevation was prevented (p<0.05) when the animals were pretreated with 7-NI before GA perfusion (24 dB SPL+/-4.2dB to 27 dB SPL+/-6.7 dB). CONCLUSION: NO mediates excitotoxicity when the cochlea is perfused with L-glutamate.     

Correlation of changes in compound action potential (CAP) tuning curves and cochlear lesion in guinea pigs after explosion

The purpose of the present study was to investigate the sensitivity of compound action potential (CAP) tuning curves to changes of the cochlear status in guinea pigs after explosion and their ability to reflect specific histological variations. The results were as follows: 1. The CAP tuning curves were abnormally broad and the Q 10 dB values were reduced by a factor of 1 after explosion, indicating wider tuning. 2. The degree of broadening of the CAP tuning curves seemed to increase as the hair cell loss increased. 3. After explosion, the tip of the tuning curve shifted to frequencies significantly higher or lower than that of the signal, it might be related to the location of hair cell loss in the cochlea. 4. In animals for which damage was restricted to only three rows of outer hair cells, changes of the CAP tuning curves were observed. It provides further evidence that the tuning properties of cochlear nerve fibers are dependent upon the integrity of the outer hair cells even though the great majority of fibers innervate inner hair cells only.     

Effects of a dopaminergic agonist in the guinea pig cochlea

This study investigates the role of dopamine, a putative lateral efferent neurotransmitter/modulator, in cochlear physiology and physiopathology. Cochlear potentials were recorded in guinea pigs after intracochlear perfusion of increasing doses (0.1–1 mM) of piribedil, an agonist of the D2/D3 receptors. A dose-dependent reduction in the amplitude of auditory nerve compound action potential (CAP) was observed, predominantly at high-intensity tone-burst stimulations, and without significant effect on CAP threshold. There was no variation of cochlear microphonic and summating potential.

When 1 mM piribedil was perfused into the cochlea during continuous 130 dB SPL pure tone exposure (6 kHz, 15 min), CAP threshold shifts were significantly less than in control animals with artificial perilymph-perfused cochleas. No dendritic damage was observed, although there was evident hair cell damage. Similarly, radial dendrites were clearly protected against ischemia-induced damage when 1 mM piribedil was applied prior to a 10-min ischemia.

These results suggests that dopamine modulates the activity of radial afferent fibers via D2/D3 receptors. The protective effect of piribedil during acoustic trauman or ischemia suggests that this modulation corresponds to a prevention of excitotoxicity due to dysfunction of inner hair cell neurotransmission.     

顺铂中毒后豚鼠耳蜗电位变化的特征及形态学实验观察

目的 观察顺铂对耳蜗微音电位（ＣＭ）、总和电位（ＳＰ）及复合动作电位（ＣＡＰ）的影响及毛细胞形态学改变。方法 用人工外淋巴液和顺铂灌流豚鼠耳蜗，分别记录耳蜗第三回中阶的ＣＭ、－ＳＰ及ＣＡＰ，琥珀酸脱氢酶染色观察毛细胞的数量变化，透射电镜观察外毛细胞结构。结果 顺铂灌流１ｈ：≤６０ｄＢ ＳＰＬ声强级刺激时ＣＭ、－ＳＰ和ＣＡＰ幅度均较灌流顺铂前略下降，≥７０ｄＢ ＳＰＬ声强级刺激时幅度比灌流顺铂前明显     

血管内皮舒张因子对豚鼠耳蜗功能的影响

目的 探讨血管内皮性一氧化氮合酶(endothelial nitric oxide synthase,eNOS)对耳蜗电位的影响.方法 健康豚鼠100只,随机等分为10组:①人工外淋巴液组;②L-精氨酸组;③Ca2+-ATP酶抑制剂组;④Ca2+-ATP酶抑制剂+L-精氨酸组;⑤Ca2+-ATP酶抑制剂+环磷酸鸟苷(c...     

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。