Distribution and change of peroxynitrite in the guinea pig cochlea following noise exposure.
Distribution and change of peroxynitrite in the guinea pig cochlea following noise exposure.
复制标题
噪声暴露后豚鼠耳蜗中过氧亚硝酸盐的分布和变化
DOI：
10.3892/br.2018.1107
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发表时间：
2018-08
影响因子：
2.3
通讯作者：
Nuttall A
中科院分区：
文献类型：
--
作者：
Han WJ;Shi XR;Nuttall A
一氧化氮（NO）介导的病理学取决于反应性中间体的形成，如过氧亚硝酸盐（ONOO−）。ONOO−可以硝酸化游离酪氨酸和蛋白质的酪氨酸残基。因此，酪氨酸硝化的增加反映了氧化应激产生的ONOO−的量。采用荧光免疫组织化学法检测了ONOO−标记物3-硝基酪氨酸（3-NT）在豚鼠Corti器和耳蜗外侧壁组织中的分布。用122 dBA宽带噪声暴露豚鼠，每天4 h，连续2d，比较正常豚鼠和噪声暴露豚鼠3-NT的免疫活性。正常动物外侧壁的外毛细胞（OHCs）、内毛细胞（IHCs）、柱细胞（PCs）、螺旋神经节细胞（SPC）和血管纹边缘细胞内均可见3-NT免疫反应阳性细胞。声音暴露增加了所有细胞中的3-NT信号，并导致广泛的外毛细胞损失。对OHC和外侧壁边缘细胞3-NT的定量分析表明，噪声暴露组OHC和外侧壁边缘细胞3-NT的免疫标记与对照组比较有显著性差异（P<0.01，n=10）。抗3-NT抗体和碘化丙啶双标记显示3-NT主要分布在OHC的顶端。此外，3-NT分布于外毛细胞和边缘细胞的核外。总之，数据表明，噪声暴露导致耳蜗外侧壁和Corti器官中ONOO−的大量产生。这与已知的增加NO生产响亮的声音应力，并表明NO衍生的自由基参与耳蜗病理生理学的噪声引起的听力损失。
Nitric oxide (NO)-mediated pathology depends on the formation of reactive intermediates, such as the peroxynitrite (ONOO−). ONOO− can nitrate free tyrosine and tyrosine residues of proteins. Therefore, increases in tyrosine nitration reflect the amount of ONOO− produced by oxidative stress. The distribution of 3-nitrotyrosine (3-NT), an ONOO− marker, in the organ of corti and the cochlear lateral wall tissue from the guinea pig were examined using fluorescence immunohistochemistry. The immunoactivity of 3-NT in the normal guinea pig was compared with animals exposed to 122dBA broadband noise, 4 h/day, for 2 consecutive days. In the normal animals, 3-NT immunoreactivity was found in the outer hair cells (OHCs), inner hair cells (IHCs), pillar cells (PCs), spiral ganglion cells (SPCs) and the marginal cells of stria vascularis in the lateral wall. Sound exposure increased the 3-NT signal in all of the cells and resulted in extensive outer hair cell loss. A quantitative analysis of the 3-NT change in OHCs and marginal cells of lateral wall showed that immunolabeling was significant (P<0.01, n=10) in the noise exposure group compared with that of the control group. Anti-3-NT and propidium iodide double labeling showed that 3-NT was distributed mainly in the apical end of OHCs. In addition, 3-NT was distributed outside of the nucleus of the OHCs and marginal cells. In conclusion, the data indicate that noise exposure leads to a significant production of ONOO− in the cochlear lateral wall and organ of corti. This is consistent with the known increase of NO production by loud sound stress and suggests that NO-derived free radicals participate in the cochlear pathophysiology of noise-induced hearing loss.