耳蜗内毛细胞突触对氨基糖甙类药物毒性的反应特性  

The cochlear ribbon synaptic response to aminoglycoside ototoxicity in C57BL/6J mice

作　　者：柳柯[1,2] 姜学钧[2] 李姝娜[3] 吴南[1] 刘会占[1] 张悦[1] 杨伟炎[1] 杨仕明[1] 

机构地区：[1]中国人民解放军总医院耳鼻喉研究所,北京100853 [2]中国医科大学附属第一医院耳鼻咽喉-头颈外科,沈阳110001 [3]江苏省镇江市第一人民医院耳鼻喉科,江苏省212002

出　　处：《中华耳科学杂志》2010年第2期162-166,共5页Chinese Journal of Otology

基　　金：国家自然科学基金面上项目(30871398);国家自然科学基金重点项目(30730040);国家863项目(2007AA02Z150)资助

摘　　要：目的探讨氨基糖甙类药物毒性对小鼠耳蜗内毛细胞突触数量的影响。方法采用固定剂量(100mg/kg)的庆大霉素对C57BL/6J小鼠每日进行腹腔注射造模,分别在注射后的第4天、7天和10天观察耳蜗基底膜顶回区域的内毛细胞突触数量的变化,以同窝未注射小鼠的耳蜗基底膜顶回作为实验对照。内毛细胞突触前后膜分别采用CtbP2和GluR2/3进行免疫荧光标记,在激光共聚焦显微镜下进行观察。采用3dmax8.0对实验结果进行三维重建,在此基础上计数耳蜗内毛细胞突触的数量。结果所有小鼠内外毛细胞均无缺失和错排,但和对照组相比,内毛细胞突触数量存在明显变化(P<0.01);其数量在庆大霉素注射第7天时达到峰值,之后明显减少。结论在氨基糖甙类药物毒性环境中,耳蜗内毛细胞突触数量表现先增加后下降的规律。这提示在氨基糖甙类药物毒性作用的过程中,内毛细胞突触数量的增加可能表明耳蜗内毛细胞带状突触存在通过改变自身数量来反映氨基糖甙类药物毒性损害的机制。Objective To investigate the early change of cochlear ribbon synapses in inner hair cells to Aminogly- coside Ototoxicity. Methods C57BL / 6J Mice were intraperitoneally injected with a dose of gentamycin（100 mg / kg） per day respectively, the apical coil of organ of Corti were studied at 4th day、 7th day、 10th day respectively （n = 5）, and the littermate untreated with gentamicin were set for control （n = 5）. RIBEYE on the presynaptic membrane and AMPA receptor on the postsynaptic membrane were labeled by CtbP2 GluR2 / 3 respectively. And three dimension restruction was performed by a application of 3ds max 8.0. Results There were no depletion of outer or inner hair cell for all groups, however, the ribbon synaptic number of cochlear inner hair cells has increased signifcantly within 7days after Gentamicin exposure （P 0.01）. and the amount of synapse number was found to decreased signifcantly and rapidly after 7day. Conclusion During the early stage of aminoglycoside ototoxicity, the more population of cochlear ribbon synapse might indicate a great down-regulation of synaptic funtion.

关 键 词：庆大霉素 耳蜗 内毛细胞突触 激光共聚焦显微镜 

分 类 号：R339.16[医药卫生—人体生理学] R978.12[医药卫生—基础医学]