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耳毒性药物:小鼠和豚鼠敏感性的差异。

Ototoxic drugs: difference in sensitivity between mice and guinea pigs.

机构信息

Department of Otolaryngology, University Hospital of Liège, Liège, Belgium.

出版信息

Toxicol Lett. 2010 Mar 1;193(1):41-9. doi: 10.1016/j.toxlet.2009.12.003. Epub 2009 Dec 14.

DOI:10.1016/j.toxlet.2009.12.003
PMID:20015469
Abstract

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n=114) and guinea pigs (n=35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss.

摘要

实验动物模型的发展在理解神经感觉性耳聋的机制和设计有效治疗方法方面发挥了不可估量的作用。本研究旨在建立一种成年小鼠耳毒性药物诱导听力损失模型,并比较成年小鼠和已充分描述的豚鼠模型的耳毒性。小鼠是一种强大的模式生物,特别是由于大量的抗体、探针和遗传突变体的可用性。在这项研究中,小鼠(n=114)和豚鼠(n=35)接受了庆大霉素或顺铂的全身治疗。听觉脑干反应显示,在耳毒性治疗开始后 2 周,豚鼠的阈值有显著的偏移,而小鼠的听力没有明显受损。毛细胞和神经元的丢失与豚鼠和小鼠的听力功能相关。这些结果表明,小鼠不是耳毒性的良好模型,在所有涉及耳毒性诱导听力损失的进一步研究中都应考虑这一点。

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