【作者】 薛桢；

【导师】 李华伟； 王宇澄； 孙珊；

【作者基本信息】 复旦大学 ， 临床医学， 2009， 硕士

【摘要】 小鼠是听力学实验常用的动物模型。听觉脑干诱发电位(ABR)是听力学检测常用的电生理学指标。随着各类转基因小鼠的广泛应用,掌握小鼠与其他啮齿类动物听力的差异是小鼠听力模型应用的基础。新霉素诱导的耳聋小鼠是听力学研究中常用的动物模型。新霉素对小鼠的耳毒性具有严格的时间选择性,我们实验室前期的工作表明,出生后第二周皮下注射新霉素致聋效果最好。为证实这一作用,本研究采用形态学、ABR检测等技术首先比较了正常小鼠、大鼠和豚鼠ABR听力学曲线和阈值,总结了小鼠的最适听力频率,并在此基础上进一步观察了新霉素对小鼠出生后第一周、第二周及第三周不同发育阶段的耳毒性作用,结果如下:1.小鼠、大鼠及豚鼠的ABR听力学曲线基本一致2.低频时(≤8 KHz)听觉阈值由低到高依次是豚鼠、大鼠、小鼠,而中高频时(≥12 KHz)小鼠听阈最低。3.小鼠出生后第二周皮下注射新霉素的耳毒性作用最强4.新霉素组小鼠毛细胞的损伤从顶圈到底圈逐步加重。由以上结果得出结论:1.小鼠具有啮齿类种属特异性脑干诱发电位频率阈值特征曲线。2.出生后第二周(P8-14)为小鼠对新霉素耳毒性最敏感的时间窗,在该时间段连续对小鼠皮下注射新霉素可建立有效的神经性耳聋模型。更多还原

【Abstract】 Mouse is a common animal model for hearing research.Auditory Brainstem Response(ABR) is a frequently used physiological test to evaluate hearing function. Due to the wide-spread research on transgenic mice,it is fundamental that we know the differences between mouse and other types of rodents about their hearing function for further research and animal model usage.Neomycin induced hearing loss in mouse is also a common animal model in hearing research.The ototoxicity of neomycin on mouse is varied by adopting time. Our previous research showed that injecting neomycin during the second week after birth may cause the most severe hearing loss among all periods after birth.In order to prove this,we used morphology and physiological examination to compare the hearing thresholds and frequency-threshold characters of normal mouse,rat and guinea pig,analyzed the best frequencies of hearing function in mouse,and observed different ototoxicity of neomycin on developing new born mouse in their first,second and third week after birth.The results are:11.Mouse,rat and guinea pig share a common frequency-threshold character.2.In low frequencies(≤8 KHz),the thresholds in turn from low to high are guinea pig,rat and mouse;while in mid and high frequencies(≥KHz), the mouse has the lowest threshold.3.The ototoxicity of neomycin on new born mouse is most severe when adopted on the second week after birth.4.The hair cell injuries become more severe from apex to base on basilar membrane.For all the results above,the conclusions are:1.Mouse has a specific Auditory Brainstem Response frequency-threshold curve/character of rodents.2.The second week after birth(P8-14) is the most sensitive time window for neomycin ototoxicity.Effective neural hearing impairment model can be established by injecting neomycin subcutaneously in this period.更多还原