药物性耳聋是儿童后天致聋因素之一。研究发现，幼年期内耳的解剖和功能成熟期间对氨基糖苷类毒性过度敏感，提示可能与内耳微环境发育有关；近年来的研究表明水通道蛋白的表达异常或功能丧失均可以引起内耳水环境的破坏进而导致听力及平衡功能的异常，我们前期的研究结果表明，内耳水通道蛋白亚型与小鼠听力发育关键期密切相关。因此我们推测水通道蛋白与药物性耳聋的发生可能存在着某种联系。本项目拟从氨基糖苷类药物代谢及水通道发育两个方面着手研究，通过免疫组织化学、分子生物学、听觉电生理学等技术，应用特异性水通道蛋白敲除的转基因小鼠模型，研究以下几个方面的内容1）水通道蛋白在内耳表达的时间和空间特点；2）新霉素的耳毒性作用与水通道蛋白在内耳表达的关系；3）改变水通道蛋白表达水平对新霉素的耳毒性作用的影响；以期揭示内耳发育关键期与耳毒性药物作用机制，并试图建立耳蜗整体培养模型，为感音神经性耳聋研究提供理论依据和研究思路。

Drug ototoxicity is the main course of hearing loss in Children. It was reported that the inner ear was hypersusceptible to the aminoglycoside antibiotics (AmAb) due to the period of anatomia structure and function development in babyhood, which suggested that the ototoxicity was related to the micro- environment of the inner ear. Recent studies explored that dysfunction of aquaporins (AQPs) will damage the water- environment of the inner ear and then produce the dysfunction of hearing and balancing. Our previous studies also revealed that the development of sub-types of AQPs in the inner ear was relative to the key period of hearing development. Therefore, we presume that there should be some relationship between Aqps and ototoxic-hearing loss. We have planned to investigate both the metabolisms of AmAb ototoxicity to the inner ear and the development of AQPs in the inner ear. We will study the following subjects by the techniques such as immunohistochemistry, molecular biology, ABR test and so on; 1) Distribution of AQPs in the inner ear during development; 2)ototoxicity of neomycin involved in the AQPs expression in the inner ear; 3) regulation of AQPs expression level affected to the ototoxicity of neomycin. Our object is to reveal the relationship between key period of inner ear development and the AmAb ototoxicity and to establish a whole organ of the cochlear culture technique, while will support the evidence of theory to the sensorineural hearing loss.