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他达那非对感音神经性聋潜伏期的影响

         

摘要

Objective To study the effects of tadalafil to the latent period of sensorineural hearing loss . Methods Total of Guinea pigs were randomly divided into a normal control group,a negative control group, a tadalafil group and a flunarizine hydrochloride group(positive control group),20 in each group.A week after white noise exposure of 120 dB,0.9% NaCl injection 4 mL/(kg· d),tadalafil 2 mg/(kg· d),and flunarizine hydrochloride 0.5 mg/(kg· d) were injected into Guinea pigs of the negative control group, tadalafil group,and flunarizine hydrochloride group respectively,continuously for 4 weeks after one week of noise exposure.The latent period( LP) of wave Ⅰand auditory brain response( ABR) were measured respec-tively prior to the experiment,1 week post-noise,1,2 and 4 weeks post-drugs.The changes of cochlea hair cells were also observed by a scan electron microscope( SEM) .Results The LP of wave Ⅰ of the normal control group at post-noise exposure,1 week,2 weeks and 4 weeks post-medication had no obvious changes from before the noise exposure,of the negative control group was significantly extended,of the tadalafil group and flunarizine hydrochloride group were both on the decline trend[(1.289 ±0.014),(1.747 ±0.020), (1.698 ±0.018),(1.628 ±0.018),(1.533 ±0.021) ms,(1.299 ±0.011),(1.760 ±0.016), (1.711 ±0.014),(1.640 ±0.015),(1.545 ±0.018) ms].The ABR of the normal control group at post-noise exposure,1 week,2 weeks and 4 weeks post-medication had no obvious changes from before the noise exposure,of the negative control group was significantly extended,of the tadalafil group and flunarizine hydro-chloride group were significantly extended after 1 week of medication and then decreased to different extents after 2 weeks of medication[(23.9 ±0.8),(41.1 ±9.9),(43.2 ±1.7),(38.8 ±1.8),(29.8 ±2.8) dB,(24.0 ±0.9),(41.1 ±9.9),(41.5 ±10.0),(39.2 ±1.7),(30.1 ±2.9) dB].SEM showed that, there were auditory hair disorder,fusion and loss of cochlea outer hair cells in the negative control group, while there was only light cochlear lesions of slight lodging and fusion of the auditory hairs in the tadalafil group and flunarizine hydrochloride group.Conclusion Tadalafil can alleviate damage of sensorineural hear-ing loss to cochlear hair cells of Guinea pigs,and shorten the extension of the LP of wave Ⅰ.%目的:探讨他达那非对感音神经性聋潜伏期的影响。方法采用随机数字表法将80只豚鼠分为正常对照组、阴性对照组、他达那非组和盐酸氟桂利嗪组(阳性对照组),各20只。阴性对照组、他达那非组、盐酸氟桂利嗪组豚鼠在白噪声暴露1周后分别腹腔注射0.9%NaCl注射液4 mL/( kg· d)、他达那非2 mg/( kg· d)、盐酸氟桂利嗪0.5 mg/( kg· d),连续给药4周。分别测试噪声暴露前1 d、噪声暴露后1、2、4周Ⅰ波潜伏期和听性脑干反应( 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。结果正常对照组豚鼠在噪声暴露后、给药1周后、给药2周后、给药4周后其Ⅰ波潜伏期较噪声暴露前基本无明显改变,阴性对照组在噪声暴露后、给药1周后、给药2周后、给药4周后后较噪声暴露前和噪声暴露后ABRⅠ波潜伏期呈延长趋势,他达那非组和盐酸氟桂利嗪组豚鼠在给药1周后、给药2周后、给药4周后较噪声暴露后ABRⅠ波潜伏期均呈下降趋势[(1.289±0.014)、(1.747±0.020)、(1.698±0.018)、(1.628±0.018)、(1.533±0.021) ms,(1.299±0.011)、(1.760±0.016)、(1.711±0.014)、(1.640±0.015)、(1.545±0.018) ms]。正常对照组豚鼠在噪声暴露后、给药1周后、给药2周后、给药4周后ABR阈值较噪声暴露前基本无明显改变,阴性对照组豚鼠噪声暴露后给药1周后ABR阈值呈延长趋势,他达那非组和盐酸氟桂利嗪组噪声暴露后给药1周后听性脑干反应阈值呈延长趋势,给药2周后其 ABR 阈值均呈不同程度下降[(23.9±0.8)、(41.1±9.9)、(43.2±1.7)、(38.8±1.8)、(29.8±2.8) dB,(24.0±0.9)、(41.1±9.9)、(41.5±10.0)、(39.2±1.7)、(30.1±2.9) dB]。扫描电镜显示,阴性对照组豚鼠耳蜗外毛细胞出现听毛紊乱、融合及缺失;而他达那非组及氟桂利嗪组耳蜗病变均较轻,听毛仅有不同程度的轻微倒伏、融合现象。结论他达那非能够减轻感音神经性聋对豚鼠耳蜗毛细胞的损害,缩短其引起的Ⅰ波潜伏期延长。

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