Takeda Taizo, Sawada Shoichi, Takeda Setsuko, Kitano Hiroya, Suzuki Mikio, Kakigi Akinobu, Takeuchi Shunji
Department of Otolaryngology, Kochi Medical School, Kohasu, Oko-cho Nankoku, Kochi 783-8505, Japan.
Hear Res. 2003 Aug;182(1-2):9-18. doi: 10.1016/s0378-5955(03)00135-7.
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 ears) 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 ears, 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<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/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.
在本研究中，进行了两项实验，以研究OPC - 31260对豚鼠实验性诱导的内淋巴积水的影响以及对大鼠内耳水通道蛋白2（AQP2）mRNA表达的调节作用。在形态学研究中，对正常豚鼠（正常耳）和三组积水耳进行定量评估，比较内耳膜长度比（IR - L）和中阶横截面积比（IR - S）的增加情况：未注入任何液体的积水耳（非注入性积水耳）、向鼓阶注入生理盐水的积水耳（注入生理盐水的积水耳）以及向鼓阶注入0.3% OPC - 31260的积水耳（注入OPC的积水耳）。实验组的IR - L明显大于正常耳组，但非注入性积水耳组、注入生理盐水的积水耳组和注入OPC的积水耳组之间无显著差异。非注入性积水耳组和注入生理盐水的积水耳组的IR - S（48.8 - 49.3%）与正常耳组（6.5%）在统计学上有差异（Dunnet多重比较检验，P<0.01）。然而，注入OPC的积水耳组的IR - S（-14.8%）明显小于非注入性积水耳组和注入生理盐水的积水耳组（单因素方差分析，P<0.01）。在定量聚合酶链反应研究中，比较了注水大鼠和注射OPC - 31260大鼠的AQP2与β - 肌动蛋白mRNA的比值（MAQP2/Mβ - 肌动蛋白）。静脉注射OPC - 31260导致耳蜗和内淋巴囊中的MAQP2/Mβ - 肌动蛋白显著降低（t检验，P<0.001）。这些结果表明，内耳的水平衡是通过血管加压素 - AQP2系统调节的，血管加压素2型拮抗剂OPC - 31260是治疗梅尼埃病的一种有前景的药物。
