年龄相关性听力损失小鼠耳蜗毛细胞的凋亡机制  

Mechanism of Hair Cell Apoptosis in Age-related Hearing Loss Mouse Cochlea

作　　者：张少强[1,2] 李胜利[2,3,4] 闫利英[1] 李随勤[1] 李白芽[3,4] 朱宏亮[3] 郑庆印 

机构地区：[1]西安交通大学医学院第一附属医院耳鼻咽喉-头颈外科,西安710061 [2]西安交通大学医学院第二附属医院耳鼻咽喉科-头颈外科 [3]西安交通大学神经科学研究中心 [4]Case Western Reserve University School of Medicine,Department of Otolaryngol-ogy Head&Neck Surgery

出　　处：《听力学及言语疾病杂志》2010年第1期43-47,共5页Journal of Audiology and Speech Pathology

基　　金：国家自然科学基金资助对外交流与合作项目(30210103151);美国NIH项目(R01DC007392);陕西省科技攻关项目(2004K16-G5)资助

摘　　要：目的观察年龄相关性听力损失小鼠耳蜗毛细胞的死亡方式,探讨老年性聋的分子机制。方法随机选用5～7只28、30和60天龄的NMF308nmf/nmf小鼠,应用ABR和DPOAE检测听功能,用免疫荧光染色组织化学技术TUNEL、Caspase-3和碘化丙啶(PI)染色标记并观察耳蜗毛细胞。结果NMF308nmf/nmf小鼠从1月龄开始发生听功能减退和毛细胞改变,到2月龄时出现明显的TUNEL阳性标记,是毛细胞凋亡的最早表现;Caspase-3阳性表达的毛细胞凋亡现象稍晚出现;PI标记可见2～3月龄开始出现毛细胞细胞核固缩和碎片;到3月龄时听功能基本丧失,耳蜗毛细胞严重缺失。结论老年性聋的早期首先出现耳蜗毛细胞出现DNA单链断裂,随后Caspase-3信号途径激活,导致耳蜗毛细胞凋亡。Objective In this study,we investigated the hair cell apoptosis and the molecular mechanisms in age-related hearing loss mouse cochlea.Methods All animals were assessed by ABR and DPOAE analysis in both ears. TUNEL （Terminal dexynucleotidyl transferase （TdT） mediated dUTP Nick End Labeling） and PI were used to identify DNA fiagments and caspase-3 activities in hair cells.Results The results showed that the nmf308 mice had progressive hair cell loss along with age. The cochlear OHCs were reduced 5%~10% at 1 month and 100% at 3 month in the basal region. Substantial amounts of TUNEL-postive OHCs nuclei were observed at age of 1 month,and activated caspase-3 labeling OHCs were most obviously observed at age of 2 months.Conclusion These results suggest that DNA single strand break is attributed primarily to apoptosis of cochlear lesion,and activation of caspase-3 at leter stage leads to the hair cell apoptiovs of nuclear condensation in age-related hearing loss mouse cochlea.

关 键 词：老年性聋 外毛细胞 凋亡 耳蜗 动物模型 

分 类 号：R764.436[医药卫生—耳鼻咽喉科]