Kitahara T, Doi K, Maekawa C, Kizawa K, Horii A, Kubo T, Kiyama H
Department of Otolaryngology, Osaka University, School of Medicine, Osaka, Japan.
J Neuroendocrinol. 2008 Dec;20(12):1295-300. doi: 10.1111/j.1365-2826.2008.01792.x.
Meniere's disease is peculiar to humans and is characterised by episodic vertigo, fluctuating hearing loss and tinnitus, and attacks of the affliction occurring under conditions of stress. Its pathology was first revealed to be inner ear hydrops through temporal bone studies in 1938. Although subsequently proposed as a disorder of water metabolism in the inner ear, its pathogenesis remains unsolved. The present study aimed to assess the link between the inner ear pathology in Meniere's disease and vasopressin, an anti-diuretic stress hormone with a potential role in inner ear fluid homeostasis. Blood samples were obtained from Meniere's disease patients in the morning, before any surgical treatment, to examine plasma vasopressin (pAVP) levels, and then from inner ear tissue during surgical treatment, to examine vasopressin type-2 receptor (V2R) in the endolymphatic sac. pAVP and the relative V2R mRNA expression in the endolymphatic sac were examined using a real-time polymerase chain reaction. Relative cAMP activity in the endolymphatic sac was also examined using tissue culture and cAMP assay. Both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5-fold versus controls; P = 0.022) were significantly higher in Meniere's patients. cAMP activity was basally up-regulated (2.1-fold versus controls) and cAMP sensitivity to vasopressin application was largely elevated (4.9-fold versus controls) in Meniere's patients. We conclude that, in the pathogenesis of inner ear hydrops, resulting in Meniere's attacks, elevation of pAVP levels (probably as a result of stress) may present as a matter of consequence, but susceptibility of the V2R-overexpressed and cAMP-hypersensitized inner ear to pAVP elevation might be essential as the basis of this disease. Further experimental and clinical studies are needed to better clarify the relationship between Meniere's disease and stress.
梅尼埃病是人类特有的疾病，其特征为发作性眩晕、波动性听力损失和耳鸣，且在应激状态下会发作。1938年通过颞骨研究首次揭示其病理为内耳积水。尽管后来有人提出这是一种内耳水代谢紊乱疾病，但其发病机制仍未解决。本研究旨在评估梅尼埃病内耳病理与血管加压素之间的联系，血管加压素是一种抗利尿应激激素，在内耳液体稳态中可能发挥作用。在任何手术治疗前的早晨采集梅尼埃病患者的血样，以检测血浆血管加压素（pAVP）水平，然后在手术治疗期间从内耳组织采集样本，检测内淋巴囊中的血管加压素2型受体（V2R）。使用实时聚合酶链反应检测内淋巴囊中pAVP和相对V2R mRNA表达。还使用组织培养和cAMP测定法检测内淋巴囊中相对cAMP活性。梅尼埃病患者的pAVP（相较于对照组升高1.6倍；P = 0.048）和内耳V2R mRNA表达（相较于对照组升高41.5倍；P = 0.022）均显著更高。梅尼埃病患者的cAMP活性在基础水平上上调（相较于对照组升高2.1倍），并且cAMP对血管加压素应用的敏感性大幅升高（相较于对照组升高4.9倍）。我们得出结论，在内耳积水导致梅尼埃病发作的发病机制中，pAVP水平升高（可能是应激的结果）可能是一个必然现象，但V2R过表达且cAMP超敏的内耳对pAVP升高的易感性可能是该疾病的发病基础。需要进一步的实验和临床研究来更好地阐明梅尼埃病与应激之间 的关系。
