Meniere's Attacks Occur in the Inner Ear with Excessive Vasopressin Type-2 Receptors

Meniere's Attacks Occur in the Inner Ear with Excessive Vasopressin Type-2 Receptors
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DOI:
10.1111/j.1365-2826.2008.01792.x
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发表时间:
2008-12-01
影响因子:
3.2
通讯作者:
Kiyama, H.
Kiyama, H.
中科院分区:
医学3区
文献类型:
--
作者:
Kitahara, T.;Doi, K.;Kiyama, H.

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梅尼埃病是人类特有的疾病,其特征是发作性眩晕、波动性听力损失和耳鸣,以及在压力条件下发生的痛苦发作。1938年,颞骨检查首次发现其病理为内耳积水。虽然后来被认为是内耳水代谢紊乱,但其发病机制仍未解决。本研究旨在评估梅尼埃病的内耳病理学与血管加压素(一种在内耳液体稳态中具有潜在作用的抗利尿应激激素)之间的联系。在任何手术治疗前的早晨从梅尼埃病患者中采集血液样品以检测血浆加压素(pAVP)水平,然后在手术治疗期间从内耳组织中采集血液样品以检测内淋巴囊中的加压素2型受体(V2 R)。实时荧光定量PCR检测内淋巴囊内pAVP和V2 R mRNA的相对表达。采用组织培养和cAMP测定法检测内淋巴囊中cAMP的相对活性。梅尼埃病患者的pAVP(1.6倍于对照组; P = 0.048)和内耳V2 R mRNA表达(41.5倍于对照组; P = 0.022)均显著升高。在梅尼埃病患者中,cAMP活性基本上调(与对照组相比为2.1倍),cAMP对加压素应用的敏感性大大升高(与对照组相比为4.9倍)。我们的结论是,在内耳水肿的发病机制,导致梅尼埃的攻击,pAVP水平的升高(可能是由于压力)可能会出现的后果,但V2 R过表达和cAMP过敏的内耳pAVP升高的敏感性可能是必不可少的基础上,这种疾病。需要进一步的实验和临床研究来更好地阐明梅尼埃病和应激之间的关系。
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-hypersensitised 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.