亨塔米辛的使用会导致内毛细胞的突触功能障碍
1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
Toxicology letters
|December 15, 2023
概括
抗生素甘他素 (Gentamicin) 通过破坏内毛细胞突触,导致听力损失. 这项研究揭示了甘他素降低了肌肉蛋白VI,损害了突触功能,导致听力受损.
科学领域:
- 耳部毒理学 耳部毒理学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 氨基糖化物引起耳毒性和听力损失,主要是通过影响头发细胞.
- 最近的证据表明,氨基糖化物也会损害内毛细胞 (IHC) 中的带状突触.
- 氨基糖化物诱导的带状突触损失的机制和功能后果尚未完全理解.
研究的目的:
- 为了研究 gentamicin 对 IHC 的带状突触的影响.
- 阐明 gentamicin 诱导的突触损伤的潜在分子机制.
- 探索突触改变对听觉功能的功能后果.
主要方法:
- 甘他素被用在C57BL/6J小鼠身上.
- 测量了听觉脑干反应 (ABR).
- 使用了免疫光染色,贴片记录和蛋白质组学.
- 西方涂抹被用来分析蛋白质表达.
主要成果:
- 亨塔米辛诱导了升高的ABR值和降低的ABR波I振幅.
- 在IHC中观察到带状突触损失.
- 补丁记录显示IHCs减少电流和改变依赖.
- 胺降低了IHCs中的肌酸VI表达的调节,影响了突触囊泡循环和外细胞形成.
结论:
- 亨塔米辛治疗导致IHCs中的突触功能障碍.
- 肌素VI的降低调节在 gentamicin 诱导的突触损伤中起着至关重要的作用.
- 这些发现强调了突触变化是氨基糖化物耳毒性的关键机制.
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