Liu Ke, Shi Chuang, Sun Yuhan, Xu Yice, Shi Lei, Shi Lin, Wang Xiaoyu, Ji Fei, Hou Zhaohui, Yang Shiming
Department of Otolaryngology, Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital , Beijing.
Acta Otolaryngol. 2014 Apr;134(4):345-51. doi: 10.3109/00016489.2013.875219. Epub 2014 Feb 12.
Dynamic distribution of ototoxic gentamicin entry into inner hair cells (IHCs) may cause an interruption of cochlear ribbon synapse.
To explore the pattern of uptake of gentamicin into IHCs, as well as its possible contribution to hearing loss.
Adult C57 mice were injected intraperitoneally with gentamicin (100 mg/kg, conjugated with Texas Red ester) continuously for 14 days. The hearing thresholds were detected by auditory brainstem response (ABR) examinations. Immunostaining and confocal microscopy were utilized to trace gentamicin distribution, as well as the expression of RIBEYE/CtBP2 in mouse IHCs. Scanning electron microscopy (SEM) observation was used to find possible alterations of stereocilia.
The distribution of gentamicin in IHCs was first found on the 4th day and the accumulation of gentamicin was increased significantly on the 7th day after treatment, corresponding to the maximal elevation of the hearing threshold. However, the accumulation of gentamicin on the 14th day did not show significant differences compared with the level found on the 7th day. In addition, the uptake of gentamicin was excessively identified at or near the synaptic ribbons of IHCs throughout the 4th, 7th, and 14th days after the treatment, suggesting that cochlear ribbon synapses could be affected by ototoxic gentamicin exposure.
耳毒性庆大霉素进入内毛细胞（IHCs）的动态分布可能导致耳蜗带状突触中断。
探讨庆大霉素进入内毛细胞的摄取模式及其对听力损失的可能影响。
成年C57小鼠连续14天腹腔注射庆大霉素（100mg/kg，与德克萨斯红酯偶联）。通过听性脑干反应（ABR）检测听力阈值。利用免疫染色和共聚焦显微镜追踪庆大霉素的分布以及小鼠内毛细胞中RIBEYE/CtBP2的表达。使用扫描电子显微镜（SEM）观察来发现静纤毛可能的改变。
庆大霉素在内毛细胞中的分布在第4天首次被发现，且在治疗后第7天庆大霉素的积累显著增加，这与听力阈值的最大升高相对应。然而，第14天庆大霉素的积累与第7天相比没有显著差异。此外，在治疗后的第4天、第7天和第14天，在内毛细胞突触带或其附近均过度检测到庆大霉素的摄取，这表明耳毒性庆大霉素暴露可能会影响耳蜗带状突触。
