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标题：Fluvastatin protects cochleae from damage by high-level noise
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作者：Claus-Peter Richter ; Hunter Young ; Sonja V. Richter 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：3033
DOI：10.1038/s41598-018-21336-7
语种：English
出版社：Springer Nature
摘要：Exposure to noise and ototoxic drugs are responsible for much of the debilitating hearing loss experienced by about 350 million people worldwide. Beyond hearing aids and cochlear implants, there have been no other FDA approved drug interventions established in the clinic that would either protect or reverse the effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear function initiated by high intensity noise. A novel synchrotron radiation based X-ray tomographic method that imaged soft tissues at micrometer resolution in unsectioned cochleae, allowed an efficient, qualitative evaluation of the three-dimensional internal structure of the intact organ. For quantitative measures, plastic embedded cochleae were sectioned followed by hair cell counting. Protection in noise-exposed cochleae is associated with retention of inner and outer hair cells. This study demonstrates the potential of HMG-CoA reductase inhibitors, already vetted in human medicine for other purposes, to protect against noise induced hearing loss.