氨基糖甙类药物毒性对耳蜗内毛细胞传入神经突触后谷氨酸受体的影响  

Aminoglycosides ototoxicity exposure induces overexpression of AMPARs at cochlear ribbon synapses of mice

作　　者：徐义策[1,2] 王雪峰[1] 柳柯[2] 施磊[3] 杨仕明[2] 

机构地区：[1]辽宁医学院附属第一医院耳鼻咽喉-头颈外科,辽宁锦州121000 [2]中国人民解放军总医院中国人民解放军耳鼻咽喉研究所,北京100853 [3]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

出　　处：《解剖科学进展》2012年第5期401-404,408,共5页Progress of Anatomical Sciences

基　　金：国家973计划重大科学研究计划干细胞项目(2012CB967900);国家973计划重大科学问题导向项目(2011CBA01000);国家自然科学基金项目(31040038);北京市自然科学基金项目(5122040);中国博士后科学基金特别资助项目(201003779);中国博士后科学基金面上项目(20100470103)

摘　　要：目的 探讨氨基糖甙类耳毒性药物暴露下小鼠内毛细胞传入神经突触后谷氨酸受体表达水平的变化,以及这种变化和小鼠听功能改变之间的关系。方法 选择5周大小的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,分别在第7天、第14天时检测受试小鼠的ABR(Click&Tone burst),并以未进行腹腔注射给药的小鼠(0d)作为对照组。使用抗GluR2/3抗体对小鼠基底膜铺片标本进行染色标记,以观察耳蜗内毛细胞传入神经突触后谷氨酸受体(GluR2/3)的表达情况。结果 注射庆大霉素小鼠在第7天、10天、14天时听力损失明显,听力阈值显著高于对照组(p<0.05)。应用庆大霉素后第7天和14天,耳蜗内毛细胞传入神经突触后谷氨酸受体(GluR2/3)的表达水平和对照组相比显著增高,听力损失最为严重,提示GluR2/3在突触后的过高表达和耳聋程度存在相关性。结论 氨基糖甙类耳毒性药物持续暴露可以造成耳蜗内毛细胞传入神经突触间隙内谷氨酸递质过表达,与耳聋程度呈正相关。Objective To investigate the alteration of AMPARs expression level at cochlear ribbon synapses induced by aminoglycosides ototoxicity exposure, as well as the possible relationship with auditory functional decline. Methods Gentamycin snlfate（100mg/kg） was injected intraperitoneally into five weeks C57BL/6J mice once a day for 14 days consecutively, the auditory function（Click ＆ Tone burst） was determined at 7th and 14th day respectively, the mice without treatment served as a control group（0d）. The cochlear basilar membranes of mice were stained by anti- GluR2/3 antibody to observe the expression alteration of AMPARs at afferent postsynaptic membrane of inner hair cells（IHCs）. Results Gentamycin sulfate injection caused the increase of hearing ABR threshold and serious damage of hearing function at 7th d, 10th d and 14th d after aminoglycosides ototoxicity exposure. In addition, the expression level of GluR2/3 was significantly increased at 7th and 14th d after aminoglycosides ototoxicity exposure compared with the control group, with positive correlation with the shifts of hearing threshold. Conclusion Aminoglycosides ototoxieity exposure could cause overexpression of glntamic acid receptor in ribbon synaptic cleft, with positive correlation with the shifts of hearing threshold.

关 键 词：氨基糖甙类药物毒性 耳蜗 内毛细胞传入神经突触 听阈 谷氨酸受体亚单位 小鼠 

分 类 号：R764.35[医药卫生—耳鼻咽喉科]