化学伴侣4-苯基丁酸可预防Cdh23erl/erl突变小鼠的听力损失和耳蜗毛细胞死亡。
Chemical chaperone 4-phenylbutyrate prevents hearing loss and cochlear hair cell death in Cdh23erl/erl mutant mice.
作者信息
Li Bo, Zheng Tihua, Yan Caifang, Wang Wenjun, Zhang Jinjin, Zhang Luping, Hu Juan, Zhang Li, Wan Yuzhu, Zhang Minyan, Zheng Qingyin
机构信息
Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, People's Republic of China.
Departments of Otolaryngology-HNS.
出版信息
Neuroreport. 2019 Feb 6;30(3):145-150. doi: 10.1097/WNR.0000000000001173.
We previously developed Cdh23 mutant mice (erl mice) as a model of hearing loss for otoprotective drug evaluation and showed that the erl mutation leads to hearing loss related to endoplasmic reticulum (ER) stress-induced cochlear hair cell apoptosis. Small molecular chemical chaperones, 4-phenylbutyrate (4PBA), targeting ER stress exert a neuroprotective effect. To evaluate whether 4PBA exerts an otoprotective effect, we intraperitoneally injected erl mice with 4PBA daily from postnatal age day 7 up to 12 weeks. Our results showed that treatment with 4PBA significantly alleviated hearing loss and suppressed hair cell death in erl mice. In addition, ER stress-related proteins were downregulated by 4PBA treatment. Our study showed that 4PBA exerts an otoprotective effect, which provides the potential to repurpose the drug for otoprotection.
我们之前培育了Cdh23突变小鼠（erl小鼠）作为听力损失模型用于耳保护药物评估，并表明erl突变导致与内质网（ER）应激诱导的耳蜗毛细胞凋亡相关的听力损失。靶向ER应激的小分子化学伴侣4-苯基丁酸盐（4PBA）具有神经保护作用。为了评估4PBA是否具有耳保护作用，我们从出生后第7天至12周每天给erl小鼠腹腔注射4PBA。我们的结果表明，4PBA治疗显著减轻了erl小鼠的听力损失并抑制了毛细胞死亡。此外，4PBA治疗下调了与ER应激相关的蛋白质。我们的研究表明，4PBA具有耳保护作用，这为将该药物重新用于耳保护提供了可能性。
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