Animal model for studying inner ear mechanism of aging

缺乏Klotho基因表达的小鼠表现出类似人类过早衰老的综合征。为了确定kl突变的小鼠纯合子（kll - kl）是否表现出听力障碍，通过光（LM）和电子显微镜（EM）的PAS反应进行了组织化学研究，并通过测量内耳静电位（EP）和内淋巴钾密度进行了生理学研究。LM研究发现血管纹中有大量具有PAS阳性反应的物质。特别是对血管纹毛细血管内皮细胞和基底膜的电镜观察。PA-TCH-SP法和PA-SP法的EM PAS反应是同一反应。PAS反应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±7.2mV）明显小于野生型小鼠（96.9±7.7mV），但Klotho小鼠（209.7±20.4mM）和野生型小鼠（207.2±26.2mM）的内淋巴钾密度几乎相等。这些结果提示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。

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.