遗传性耳聋基因对噪声反应的研究  

The responses of hereditary hearing loss genes to acoustic injury

作　　者：杨淑芝[1,3] 蔡群峰 董有毅 杨卫平[2,3] 胡博华 

机构地区：[1]解放军总医院第一附属医院耳鼻咽喉科,北京100048 [2]解放军总医院耳鼻咽喉头颈外科,耳鼻咽喉研究所,北京100853 [3]美国纽约州立布法罗大学听力耳聋中心,美国14214

出　　处：《中华耳科学杂志》2016年第6期719-724,共6页Chinese Journal of Otology

基　　金：美国国立卫生院耳聋和其他交流障碍国立研究所RO1项目(RO1DC010154 to BH Hu)

摘　　要：目的探讨噪声性聋小鼠动物模型中遗传性耳聋相关基因表达的变化,以了解这些基因是否参与耳蜗对噪声的反应。方法根据已知的人类耳聋基因挑选出92个同类小鼠基因,检查这些基因对噪声损伤的反应。8只小鼠(雌雄各半,4周龄)接受持续噪声暴露(1-7k Hz,120d B SPL)1小时,造成耳蜗的急性声损伤。ABR检测听力变化,荧光染色原位观察耳蜗毛细胞损伤情况,q RT-PCR检测耳聋基因表达变化。结果在92个检测基因中,86个基因在耳蜗组织中表达。噪声暴露后ABR检测显示所有检测频率的ABR阈值明显提高(P<0.001)。免疫荧光染色原位观察结果显示噪声暴露后耳蜗底转外毛细胞缺失。q RT-PCR检测显示共有6个基因的表达差异具有统计学意义(P<0.05),其中表达下调的基因有4个,分别是Col4a5、P2rx2、Tmc1、Tprn,表达上调的基因有2个,分别是Ndp和Smpx。这些基因参与多种细胞功能。结论噪声性聋是一个复杂的退化过程,除环境因素外,多种耳聋基因参与其发病。Objective To determine the response of hereditary hearing loss genes to acoustic injury in mice. Methods Eight C57BL/6J mice （4 males and 4 females, 4 weeks old） were randomly divided into a control and a noise group. The noise group subjects were exposed to a broadband noise at 120 dB SPL for 1 hour. ABR thresholds were measured and missing outer hair cells were quantified to determine the level of cochlear damage 1 day after noise exposure, qRT-PCR arrays were used to determine the expression levels of 92 genes that have been identified in human as hereditary hearing loss genes. Results ABR measurements showed a significant increase in threshold after the noise exposure （P〈0.001） and pathological assessment revealed outer hair cell lesions in the basal turn of the cochlea. Gene expression analysis identified 6 genes that displayed significant expression changes. Among these genes, four （Co14a5, P2rx2, Tmc1, and Tprn） were down-regulated, and two （Ndp and Smpx） were up-regulated. These genes participate in various cellular functions. Conclusion Noise-induced cochlear damage is a complex degenerative process and multiple deafness genes are involved in its etiology.

关 键 词：噪声性聋 遗传性聋 基因 小鼠 MRNA表达 

分 类 号：R764[医药卫生—耳鼻咽喉科]