Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.
Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.
复制标题
牛磺熊去氧胆酸可预防 Cdh23erl/erl 小鼠的听力损失和毛细胞死亡
DOI：
10.1016/j.neuroscience.2015.12.050
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发表时间：
2016-03-01
期刊：
影响因子：
3.3
通讯作者：
Zheng QY
中科院分区：
文献类型：
--
作者：
Hu J;Xu M;Yuan J;Li B;Entenman S;Yu H;Zheng QY
多年来，感音神经性耳聋一直是实验和临床研究的主题。最近发现的CDH23基因新突变，CDH23erl/erl，被证明是人类常染色体隐性遗传性非综合征耳聋(DFNB12)的小鼠模型。牛磺酸脱氧胆酸(TUDCA)是一种牛磺酸偶联胆汁酸，已被用于肝病、糖尿病、神经退行性疾病和其他与细胞凋亡相关的疾病的实验研究和临床应用。由于毛细胞凋亡被认为是导致CDh23erl/erl小鼠(erl小鼠)听力损失的细胞机制，因此本研究探讨了TUDCA对erl小鼠的耳保护作用：预防听力障碍和保护毛细胞死亡。我们的结果表明，TUDCA的全身治疗显著减轻了ERL小鼠的听力损失，并抑制了毛细胞死亡。此外，TUDCA还可抑制ERL小鼠耳蜗组织中的凋亡基因和caspase-3的激活。提示TUDCA有可能成为治疗人DFNB12的潜在药物。
Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cdh23 gene, Cdh23erl/erl, was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23erl/erl mice (erl mice), this study investigated TUDCA’s otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12.