Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice
Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice
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DOI：
10.1016/j.heares.2005.05.010
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发表时间：
2005-10-01
期刊：
影响因子：
2.8
通讯作者：
Yoo, TJ
中科院分区：
文献类型：
--
作者：
Guo, YK;Zhang, CX;Yoo, TJ
高脂血症和感音神经性听力损失之间的关系仍然不清楚。在这项研究中，我们首次阐明了载脂蛋白-E 敲除 (ApoE-KO) 小鼠的耳蜗形态和听觉改变及其与高脂血症、动脉粥样硬化和内皮功能障碍的关系。十周大的 ApoE-KO 小鼠喂食动脉粥样硬化饮食（1.25% 胆固醇）或正常饮食。野生型小鼠（C57BL/6J）作为正常对照。 14周后，与C57BL/6J小鼠相比，ApoE-KO小鼠出现明显的高脂血症、动脉粥样硬化、内皮功能障碍和听力障碍，尤其是高频听力障碍（P < 0.001）。研究发现，听力损失与动脉粥样硬化程度和血浆总胆固醇水平之间存在高度正相关。所有 ApoE-KO 小鼠均检测到听力损失，尤其是高频听力损失。毛细胞损失主要发生在基转处，血管内膜增厚，耳蜗螺旋动脉（SMA）管腔狭窄；动脉粥样硬化饮食加剧了这些组织学变化。此外，ApoE-KO 小鼠主动脉壁和耳蜗中的内皮一氧化氮合酶 (eNOS) 明显减少。这些结果表明高脂血症和动脉粥样硬化可以引起耳蜗形态和功能的改变。 SMA 狭窄可能导致耳蜗缺血缺氧、内皮功能障碍和 eNOS 活性低，从而导致听力损失。 (c) 2005 Elsevier B.V. 保留所有权利。
The relationship between hyperlipidemia and sensorineural hearing loss remains obscure. In this study, we elucidate for the first time the cochlear morphological and auditory alterations and their relationships with hyperlipidemia, atherosclerosis, and endothelial dysfunction in apolipoprotem-E knockout (ApoE-KO) mice. Ten-week-old ApoE-KO mice were fed either atherosclerotic diet (1.25% cholesterol) or normal diet. Wild type mice (C57BL/6J) served as normal controls. Fourteen weeks later, marked hyperlipidemia, atherosclerosis, endothelial dysfunction, and hearing impairment, especially in the high frequencies, had developed in ApoE-KO mice as compared with C57BL/6J mice (P < 0.001). A high positive correlation between hearing loss and the extent of atherosclerosis and plasma total cholesterol levels was found. Hearing loss, especially at high frequencies, was detected in all ApoE-KO mice. Hair cell loss mainly at the base turn, thickening of vascular intima, and lumen stenosis of the spiral modiolar artery (SMA) in cochlea were also found; these histological changes were exacerbated by the atherosclerotic diet. Furthermore, endothelial nitric oxide synthase (eNOS) in aortic wall and cochlea was distinctly reduced in ApoE-KO mice. These results demonstrate that hyperlipidemia and atherosclerosis can induce alterations in cochlear morphology and function. The stenosis of SMA, which may cause cochlear ischemia and hypoxia, endothelial dysfunction, and low eNOS activity, may contribute to hearing loss. (c) 2005 Elsevier B.V. All rights reserved.