阿米卡星对幼年大鼠内耳毒性实验观察

Ototoxicity of amikacin to inner ear of infant rats

目的探讨阿米卡星对幼年大鼠内耳的毒性作用。方法实验组9天龄SD大鼠皮下注射500mg·kg-1·d-1阿米卡星连续1周,对照组皮下注射0.9%生理盐水连续1周。分别于用药后1天、1周和3周行听觉脑干反应测听(ABR)仪测试实验组和对照组大鼠耳蜗听功能,并对耳蜗进行扫描电镜观察和常规切片观察。结果实验组大鼠ABR阈值,用药后1天与对照组比较、用药后1周与用药后1天和对照组比较,差异均有统计学意义(P<0.01),而用药后3周和用药后1周比较,差异无统计学意义(P>0.05)。形态学观察,随用药后时间延长,柯替器细胞损伤从感觉毛细胞到非感觉支持细胞,用药后3周出现立方上皮样结构。实验组大鼠无前庭功能障碍。结论阿米卡星连续用药可导致幼年大鼠耳蜗毛细胞的严重损伤,而对前庭功能影响较小。

Objective To investigate the ototoxicity of Amikacin to infant rats. Methods Nine-day-old rats were treated hypodermically with amikaein 500 mg·kg^-1·d-1 for 7 successive days. Auditory brainstem response audiometry （ABR） was recorded to monitor the animals hearing levels at the 1th day, the 1th week, and the lth month of the drug administration, respectively. Histopathological changes were observed by using scanning electron microscopy and light microscopy. The control was administration by physiological saline. Results ABR monitoring showed that profound hearing loss was both bilateral and permanent. There was a statistically significant threshold shift between the lth day, the lth week of medicine administration and the control （P 〈 0.01）. No statistical differences were observed of ABR threshold between the lth month and the hh week of amikacin administration （P〉 0.05）. Histopathologieal examination showed the loss of cells in the organ of Corti from sensory hair cells to non-sensory supporting cells after amikaein administration and the euboidal epithelium was observed at the end of 1 month after administration. There were no symptoms of vestibular dysfunction. Conclusion Amikacin induces severe damage on cochlear hair cell of infant rats, however, there is no significant affection on vestibular function.