PROSTAGLANDIN E RECEPTOR SUBTYPE EP4 AGONIST PROTECTS COCHLEAE AGAINST NOISE-INDUCED TRAUMA
PROSTAGLANDIN E RECEPTOR SUBTYPE EP4 AGONIST PROTECTS COCHLEAE AGAINST NOISE-INDUCED TRAUMA
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DOI：
10.1016/j.neuroscience.2009.03.014
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发表时间：
2009-06-02
期刊：
影响因子：
3.3
通讯作者：
Ito, J.
中科院分区：
文献类型：
--
作者：
Hori, R.;Nakagawa, T.;Ito, J.
前列腺素E-1常用于急性感音神经性听力损失的临床治疗。然而，前列腺素E-1对内耳的作用机制尚未阐明。前列腺素E-1的生理作用由前列腺素类受体前列腺素I受体和前列腺素E受体亚型EP 1、EP 2、EP 3和EP 4介导，其各自的激动剂已被纯化。在目前的研究中，我们检查了局部应用EP 4激动剂治疗感音神经性听力损失的疗效。我们用逆转录-聚合酶链反应和免疫组织化学方法检测了小鼠耳蜗中EP 4的表达。采用听觉脑干反应和组织学分析的方法，对噪声暴露前后局部给予EP 4激动剂的保护作用进行了测试。结果表明，EP 4在耳蜗中的表达，并表明，前和后处理与EP 4激动剂显着衰减听觉脑干反应的阈值偏移，并显着衰减外毛细胞的损失被发现在局部EP 4激动剂治疗噪声暴露前。这些发现表明，EP 4参与前列腺素El作用于耳蜗的机制，并且局部EP 4激动剂治疗可以减轻急性感音神经性听力损失。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Prostaglandin E-1 is frequently used for the clinical treatment of acute sensorineural hearing loss. However, the mechanisms underlying the effects of prostaglandin E-1 on the inner ear have not yet been elucidated. The physiological effects of prostaglandin E-1 are mediated by the prostanoid receptors prostaglandin I receptor and the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, the respective agonists for which have been purified. In the current study, we examined the efficacy of a local EP4 agonist application for the treatment of sensorineural hearing loss. We examined EP4 expression in the mouse cochlea using the reverse transcription-polymerase chain reaction and immunohistochemistry. The protective effects of local EP4 agonist treatment before or after noise exposure were tested in guinea pigs using measurements of auditory brain-stem responses and histological analysis. The results demonstrated EP4 expression in the cochlea, and showed that pre- and post-treatment with an EP4 agonist significantly attenuated threshold shifts of auditory brain stem responses, and significant attenuation in the loss of outer hair cells was found in local EP4 agonist treatment before noise exposure. These findings indicate that EP4 is involved in mechanisms for prostaglandin El actions on the cochlea, and local EP4 agonist treatment could attenuate acute sensorineural hearing loss. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.