Investigation of roles of nitric oxide in age-related cen aninemal hearing loss n Ring mock-out mice and its clinical application

与年龄相关的听力损失会降低老年人的生活质量。预防和治疗老年性听力损失是一项重要而紧迫的任务。我们以C57BIJ8小鼠作为年龄相关性听力损失的实验模型，通过听觉脑干（ABR）反应来研究听觉功能。光镜下用免疫组织化学方法观察内耳一氧化氮和自由基相关物质的变化。ABE显示，7-8月龄小鼠和12月龄小鼠的听力水平比7周龄小鼠差。12月龄小鼠的听力水平比7-8月龄小鼠差。与12月龄小鼠相比，7 ~ 8月龄小鼠耳蜗Corti脏器、螺旋神经节细胞和侧壁中诱导型NO合成酶（NOS）和强自由基过氧亚硝酸盐标志物硝基酪氨酸的表达明显增强。提示一氧化氮和氧化应激与老年小鼠耳蜗细胞损伤和细胞死亡有关。与野生型相比，NOS基因缺失的小鼠随着年龄的增长，听力水平往往更差，这表明NOS对与年龄相关的耳鸣有保护作用。活化的Alit （phospho-Akt）通过激活内皮细胞NOS （eNOS）影响NO的产生。本实验在耳蜗和前庭中观察到Akt的表达。这表明磷酸化akt与内源性生存信号有关。

Age-related hearing loss decreases quality of life of elderly people. Prevention and treatment of age-related hearing loss are important and urgent tasks. We investigated auditory function by auditory brain stem (ABR) responses, using C57BIJ8 mice as an experimental model of age-related hearing loss. We observed changes of nitric oxide and free-radical related substances in the inner ear using an immunohistcehemical method under a light microscope. ABE demonstrated that hearing levels of 7-8 month-old mice and 12 month-old mice were worse than those of 7 week-old mice. Hearing levels of 12 month-old mice were worse than those of 7-8 month-old mice. Expressions of inducible type NO synthase (NOS) and nitrotyrosine, a marker of peroxynitrite which is a strong radical, were enhanced in Corti organ, spiral ganglion cells and lateral wall of cochleae in 7-8 month-old mice, compared with 12 month-old mice. These results suggest that NO and oxidative stress is associated with cell damage and cell death of cochleae of aged mice. Hearing levels of mice with NOS gene deletion tend to be worse, as they grow old, compared with wild type, suggesting that NOS functions in a protective way for age-related heaving Ices. Active firm of Alit (phospho-Akt) influences NO production by activation of endothelial NOS (eNOS). Expression of Akt was observed in cochlea and vestibule in our experiments. This suggested that phospho-Akt is associated with survival signal in the inner eat.