The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops
The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops
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DOI：
10.1016/s0378-5955(03)00135-7
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发表时间：
2003-08-01
期刊：
影响因子：
2.8
通讯作者：
Takeuchi, S
中科院分区：
文献类型：
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作者：
Takeda, T;Sawada, S;Takeuchi, S
本研究通过两个实验探讨OPC-31260对豚鼠内淋巴积水的影响及对大鼠内耳水通道蛋白-2（AQP 2）mRNA表达的调节作用。在形态学研究中，定量评估了正常豚鼠的Reissner膜长度（IR-L）和中阶横截面积（IR-S）的比值的增加（正常耳）和三组积水耳：耳积水不输液（非输液积水耳），鼓室阶灌注生理盐水的耳积水（盐水灌注的积水汽车）和将0.3%OPC-31260灌注到鼓阶中的积水耳（OPC灌注的积水耳）。各实验组的IR-Ls均明显大于正常耳组，但未灌注积水汽车组、盐水灌注积水耳组和OPC灌注积水耳组间差异无统计学意义。非灌注性积水耳和盐水灌注性积水耳的IR-Ss（48.8-49.3%）与正常耳的IR-Ss（6.5%）比较，差异有统计学意义（Dunnet多重比较检验，P < 0.01）。灌注OPC的积水耳的IR-S（-14.8%）显著小于未灌注积水耳和盐水灌注积水耳（单因素方差分析，P <0.01）。在定量聚合酶链反应研究中，比较了水注射和OPC-31260注射大鼠之间AQP 2和β-肌动蛋白mRNA的比例（M-AQP 2/Mbeta-actin）。静脉注射OPC-31260后，耳蜗和内淋巴囊内M-AQP 2/ Mbeta-actin均显著降低（t检验，P < 0.001）。这些结果表明，水稳态在内耳的调节通过加压素-AQP 2系统，加压素2型拮抗剂OPC-31260是一种有前途的药物在治疗梅尼埃病。(C)2003 Elsevier B. V.保留所有权利。
In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic cars) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic cars, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P < 0.01). However, IR-S of the OPC-infused hydropic ears (- 14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P < 0.0 1). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (M-AQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in M-AQP2/ Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P < 0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease. (C) 2003 Elsevier B.V. All rights reserved.