耳毒性药物对小鼠耳蜗外毛细胞prestin表达的影响  

Ototoxic aminoglycoside exposure causes abnormal expression of prestin in cochlear outer hair cells of mice

作　　者：赵宁[1] 柳柯[1,2] 杨仕明[2] 王小宇[2] 石闯[1,2] 施磊[1] 姜学钧[1] 

机构地区：[1]中国医科大学附属第一医院耳鼻咽喉-头颈外科,辽宁沈阳110001 [2]中国人民解放军总医院耳鼻咽喉-头颈外科,中国人民解放军耳鼻咽喉研究所,北京100853

出　　处：《解剖科学进展》2013年第3期250-254,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金项目(No.31040038);北京市自然科学基金项目(No.5122040);中国博士后科学基金项目(No.201003779;20100470103);辽宁省科技计划项目(No.2011225017;2012225021)

摘　　要：目的探讨氨基糖甙类药物庆大霉素对小鼠外毛细胞马达蛋白prestin的影响以及和听力损害之间的关系。方法选择鼠龄为5周的C57BL/6J小鼠,每天腹腔注射庆大霉素1次,药物浓度为100mg/kg,连续给药14d。实验期间,分别在第4d,7d和第14d时检测受试小鼠的ABR(Click)以观察耳毒性药物对小鼠听功能的影响,并以未进行腹腔注射给药的小鼠(0d)作为对照组。采用免疫组织化学结合激光共聚焦显微镜方法,观察小鼠耳蜗基底膜铺片标本上prestin表达变化,并采用比较荧光强度的方法定量分析prestin在各组之间表达量的差异。结果听功能检测显示,实验组小鼠听力在第4d时开始下降,到第7d时下降达到峰值(P<0.01),14d时较第7d有所降低但无显著差异(P>0.05),但仍高于对照组(P<0.05)。prestin在外毛细胞表达量在第4d开始上调,表现为圆环状的绿色荧光变得模糊,第7d时圆环的形状已经变得不规则并且多带有比较长的尾迹,而prestin表达量达到了最高水平(P<0.01),第14d时表达量和第7d相比有所降低(P<0.05),但是仍然高于对照组(P<0.05)。结论氨基糖甙类耳毒性药物持续暴露导致prestin过表达,与小鼠的听力损害过程存在一致性,提示prestin过表达可能参与致聋过程。Objective To investigate the expressional alterations of prestin in cochlear outer hair cells（OHCs） to explore its relationship with hearing loss in response to ototoxic aminoglycosides exposure. Methods Five weeks C57BL/6J mice were injected intraperitoneally with a low dose of gentamicin （100mg/kg） for 14 days. The hearing function（click） was tested at the 4d, 7d, and 14d respectively, the mice without administration of gentamicin as a control（0d）. The profiles of prestin in the OHCs of cochlear basilar membrane were determined by immunostaining and confocal microscopy and analyzed quantitatively by the ratio of optical density（OD）. Results The ABR threshold was increased at 4d, reached the highest at 7d, then decreased slightly at 14d after aminoglycosides otoxicity exposure, but still higher than normal control（P〈0.01）. The expression level of prestin in outer hair cells began to increase at 4d, reached the highest at 7d and then decreased a little at 14d after aminoglycosides otoxicity exposure but still higher than normal control（P〈0.01）. Conclusion Ototoxic aminoglycosides exposure causes the overexpression of prestin in outer hair cells, which is correspondent to the hearing threshold shifts, indicating that prestin might be involved in the pathological process of heating loss caused by ototoxic aminoglycosides exposure.

关 键 词：氨基糖甙类药物毒性 耳蜗 外毛细胞 PRESTIN 小鼠 

分 类 号：R322.923[医药卫生—人体解剖和组织胚胎学]