Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Lab Invest. 2013 Sep;93(9):1001-11. doi: 10.1038/labinvest.2013.91. Epub 2013 Jul 22.
The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Ménière's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD.
本研究旨在通过建立新的动物模型，阐明梅尼埃病（Ménière's disease，MD）眩晕发作的潜在机制，并深入了解内耳水稳态。我们对豚鼠前庭系统进行了组织病理学和功能评估。在第一个实验中，所有动物在左耳内淋巴囊电灼后 1 或 4 周时，给予生理盐水或去氨加压素（血管加压素 2 型受体激动剂），然后取双耳颞骨，定量评估内淋巴积水程度。在第二个实验中，手术 1 或 4 周后，动物在给予生理盐水或去氨加压素后评估平衡障碍和眼球震颤。在第一个实验中，与其他组相比，手术 4 周后给予去氨加压素的动物耳蜗和椭圆囊内淋巴间隙比例显著增加。在第二个实验中，所有接受手术并给予去氨加压素的动物均出现自发性眼球震颤和平衡障碍，而所有接受手术但未给予去氨加压素的动物均无症状。我们的动物模型在耳蜗和椭圆囊中诱导出严重的内淋巴积水，并出现平衡障碍和自发性眼球震颤发作。这些发现表明，去氨加压素的给药可能会由于急性 V2（血管加压素 2 型受体）介导的作用而加剧内淋巴积水，并且当与内淋巴囊功能障碍结合时，可能导致类似于 MD 患者眩晕发作的暂时前庭异常。
