Animal model for studying inner ear mechanism of aging

研究内耳衰老机制的动物模型

• 批准号: 12671674
• 负责人: TORIHARA Koji
• 金额: $ 0.64万
• 依托单位: MIYAZAKI MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671674/
• 关键词: Klotho mice; potassium dencity; EP; Presbyacusis; aging; 老化; 内耳形態

Mice deficient in Klotho gene expression exhibit a syndrome resembling premature human aging. To determine whether mouse homozygotes for the kl mutation (kll kl) show hearing dysfunction, histochemical study by the PAS reaction with light (LM) and electon microscopy (EM), and physiological study by measurement of the endocochleal static potential (EP) and potassium density in endolymph. The substances with PAS positive raction are found in large amounts in the stria vascularis with LM study. Especially, the endothelial cell and the basement membrane of capillaries in stria vascularis with EM study. The both of EM PAS reactions with the PA-TCH-SP method and the PA-SP method are the same reaction. The existence of PAS reactive substances might be associated with vascular endothelial dysfunction. We demonstrate that the EP of Klotho mice is significantly smaller (80.9 ± 7.2mV) than the EP of wild-type mice (96.9 ± 7.7mV), however, potassium densities in endolymph between klotho mice (209.7 ± 20.4mM) and wild-type mice (207.2 ± 26.2mM) are almost equivalent. These results suggest a decrease in EP is associated with stria vascularis dysfunction. The process of presbyacusis might be a reflection of stria vascularis dysfunction caused by aging.

Klotho基因表达缺陷的小鼠表现出一种类似于人类过早衰老的综合征。为了确定KL突变纯合子(Kll KL)是否存在听力障碍，采用PAS光镜和电子显微镜组织化学方法进行了研究，并通过测定耳蜗内静态电位(EP)和内淋巴钾浓度进行了生理学研究。光镜下可见血管纹内有大量PAS阳性反应物质。尤其是血管纹内皮细胞和毛细血管基底膜的光镜观察。用PA-TCH-SP法和PA-SP法进行的EM PAS反应均为同一反应。PAS活性物质的存在可能与血管内皮功能障碍有关。结果表明，Klotho小鼠的EP(80.9±7.2 mV)明显小于野生型小鼠(96.9±7.7 mV)，而Klotho小鼠(209.7±20.4 mM)和野生型小鼠(207.2±26.2 mM)内淋巴的钾密度基本相同。这些结果表明，EP的降低与血管纹功能障碍有关。老年性耳聋的过程可能是衰老引起的血管纹功能障碍的反映。