联合应用卡那霉素和速尿的豚鼠耳蜗毒性实验观察

Ototoxicity of co-administration of kanamycin and furosemideto guinea pigs

目的探讨卡那霉素和速尿联合用药对豚鼠耳蜗的毒性作用。方法实验组25只豚鼠先行肌肉注射卡那霉素500mg/kg,2小时后静脉注射速尿50mg/kg,对照组4只豚鼠。于药物注射后7天行听觉脑干诱发电位(ABR)仪检测试验组和对照组豚鼠耳蜗听功能,对阈值大于95dBSPL豚鼠行耳蜗铺片免疫荧光染色和常规切片观察,并对耳蜗进行扫描电镜观察。结果实验组25只豚鼠中有13只豚鼠ABR测试阈值高于95dBSPL,将这些致聋豚鼠作为观察对象,发现毛细胞和神经纤维明显受损,以耳蜗第一、二回损伤明显。结论卡那霉素和速尿联合用药可导致豚鼠毛细胞和神经纤维严重受损,是建立耳聋模型的一种快速而有效的方法。

Objective To investigate the ototoxicity of co-administration of kanamycin （KM） with the loop diuretic furosemide to guinea pigs. Methods Guinea pigs received an intramuscular injection of KM （500 mg/kg） followed 2h later by an intravenous infusion of furosemide（50 mg/kg）. Auditory brainstem responses（ABRs） were recorded to monitor the animals＇ hearing at the 7th day after the drug administration. Immunohistochemical and histopathological changes were observed by using light microscopy and scanning electron microscopy. Results Subsequent ABR monitoring showed that profound hearing loss was both bilateral and permanent. Histopathological examination showed an absence of all inner and outer hair cells in the basal cochlea. The extent of neurofiber lesion was also eveident at the basal cochlea and dependent on the period of survival following the deafening procedure. Conclusion The co-administration of KA and furosemide effectively produces a profound hearing loss in guinea pigs and it is an effective deafening method for acute animal experiments.