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硫酸卡那霉素对成年大鼠的耳毒性效应

张志存, 余洪猛^*, 刘全, 田洁, 王天丰, 赖垂金, 周晓娅

复旦大学附属眼耳鼻喉科医院耳鼻喉科；中心实验室，上海 200031；复旦大学脑科学研究院，上海 200032

摘要

本研究旨在观察硫酸卡那霉素(kanamycin sulfate, KM)对成年大鼠的耳毒性效应。6~7周龄的雄性Sprague-Dawley (SD)大鼠40只，随机分为2组：实验组，每天腹腔注射KM (500 mg/kg) 2周；对照组，注射等量生理盐水2周。通过检测脑干听觉诱发电位(auditory brainstem response, ABR)观察大鼠听力改变。ABR检测结束后，分离出耳蜗进行基底膜铺片、耳蜗冰冻切片，观察耳蜗螺旋神经节细胞(spiral ganglion cells, SGCs)的密度和耳蜗形态学改变。结果显示，注射KM 2周后，大鼠在各频率的听觉阈值均有明显升高，其上升幅度超过60 dB；随着时间推移，KM组SGCs密度逐渐降低，Corti器结构尚存，但外毛细胞及内毛细胞均有不同程度的缺失，以外毛细胞为甚；内毛细胞缺失与SGCs的密度下降相平行。以上结果表明，6~7周龄大鼠经过KM作用2周后，听力会明显下降，达到重度耳聋甚至全聋。KM的耳毒性作用与SGCs和内外毛细胞的损伤密切相关。

关键词： 硫酸卡那霉素; 耳聋; 脑干听觉诱发电位; 大鼠

分类号：R339.16

[Ototoxicity of kanamycin sulfate in adult rats and its underlying mechanisms.] [Article in Chinese]

ZHANG Zhi-Cun, YU Hong-Meng^*, LIU Quan, TIAN Jie, WANG Tian-Feng, LAI Chui-Jin, ZHOU Xiao-Ya

Department of Otolaryngology and Central Laboratory, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, China； The Institutes of Brain Science, Fudan University, Shanghai 200032, China

Abstract

The aim of the present study was to assess the ototoxicity of kanamycin sulfate (KM) in adult rats and its underlying mechanism. Forty male Sprague-Dawley rats (6–7 weeks old) were randomly divided into the experimental group and the control group. The animals in the experimental group were injected subcutaneously with KM (500 mg/kg per day) for two weeks, and the control group received equal volume of normal saline. To assess the ototoxicity of KM, the auditory brainstem response (ABR) was recorded to monitor the changes in hearing thresholds, and the density of spiral ganglion cells (SGCs) and morphology of cochlea were observed using surface preparations and frozen sections of cochlea. The results showed that the hearing threshold of rats in the experimental group was elevated by more than 60 dB across all the frequencies two weeks after the first administration of KM. And in the experimental group, the density of SGCs became lower, and organ of Corti suffered loss of hair cells. The loss of outer hair cells (OHCs) was more severe than that of inner hair cells (IHCs), correlated with the density decrease of SGCs. We conclude that the ototoxicity of KM in the adult rats was apparent and the underlying mechanism is associated with the loss of SGCs and hair cells.

Key words: kanamycin sulfate; hearing loss; auditory brainstem response; rat

收稿日期：2010-10-12　　录用日期：2011-02-18

通讯作者：余洪猛　　E-mail: hongmengyush@yahoo.com.cn

引用本文：

张志存, 余洪猛, 刘全, 田洁, 王天丰, 赖垂金, 周晓娅. 硫酸卡那霉素对成年大鼠的耳毒性效应[J]. 生理学报 2011; 63 (2): 171-176.

ZHANG Zhi-Cun, YU Hong-Meng, LIU Quan, TIAN Jie, WANG Tian-Feng, LAI Chui-Jin, ZHOU Xiao-Ya. [Ototoxicity of kanamycin sulfate in adult rats and its underlying mechanisms.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (2): 171-176 (in Chinese with English abstract).