年龄相关听力损失小鼠耳蜗毛细胞的凋亡抑制剂治疗研究  

Mechanism of apoptosis of hair cell in the cochlea of age-related hearing loss

作　　者：张正民[1] 李胜利[1,2] 

机构地区：[1]西安交通大学医学院第二附属医院耳鼻喉科,西安710004 [2]西安交通大学医学院神经科学研究中心

出　　处：《陕西医学杂志》2011年第9期1107-1111,共5页Shaanxi Medical Journal

基　　金：国家自然科学基金资助对外交流与合作项目(No30210103151);美国NIH项目(NoR01DC007392);陕西省科技攻关项目(No2004K16-G5)

摘　　要：目的:观察年龄相关听力损失耳蜗毛细胞的死亡方式,探讨防治老年性耳聋的分子机制。方法:将NMF308nmf/nmf小鼠做为年龄相关听力损失动物模型,每组随机选择7只28d,30d和60d的NMF308nmf/nmf小鼠,用ABR和DPOAE测定听觉功能,用免疫荧光染色组织化学技术TUNEL,Caspase-3和PI(碘化丙啶)染色标记耳蜗毛细胞。结果:NMF308nmf/nmf小鼠从1月龄开始发生听力减退和毛细胞功能改变,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激活表达的毛细胞凋亡现象稍晚出现;PI标记可见毛细胞细胞核固缩和碎片出现的时间从2月龄开始;到3月龄时该种小鼠听力基本丧失,耳蜗毛细胞严重缺失。结论:在老年性耳聋早期,首先出现DNA单链断裂,随后有Caspase-3信号途径的激活,导致耳蜗毛细胞凋亡是老年性耳聋的主要分子机制。Objective：Age-related hearing loss（Presbycusis） is the most common type of sensory impairment in human being.However,the molecular mechanisms of the presbycusis remain unclear.Apoptosis of outer hair cells（OHCs） in the cochlea has been found in aging animals.Methods：In this study,we investigated the apoptosis of hair cell in the cochlea of age-related hearing loss generated by ENU mutagenesis.Results： The results showed that the nmf308 mice with progressive hair cell loss along a base to apex gradient with age-related hearing loss.The cochlear OHCs reduced from 5-10% at 1 month to 100% at 3 month in the basal region.Substantial amounts of TUNEL-postive OHCs nuclei appeared at 1 month age,and activated caspase-3 labeling demonstrated that most OHCs appeared at 2 months age.Conclusion： These result suggest that DNA single strand break is attributed primarily to apoptosis of cochlear lesion,whereas the later stage of lesion expansion leads to activation of caspase-3 activity reduced with further progression of nuclear condensation in age-related hearing loss.

关 键 词：听力受损者/病理生理学 年龄因素 毛细胞 细胞凋亡 耳蜗 模型 动物 小鼠 

分 类 号：R363.23[医药卫生—病理学]