Morimoto Yasuo, Aozuka Yasushi, Shibata Yujiro
Kampo Research Laboratories, Kracie Pharma, Ltd., Toyama, Japan.
Yakugaku Zasshi. 2011;131(8):1241-50. doi: 10.1248/yakushi.131.1241.
Hot flash (HF) is the most common phenomenon in climacteric symptoms which often develop concomitantly with a decrease in estrogen in postmenopausal women. The onset mechanism of the hot flash is complicated and remains unclear. To date, some animal models of postmenopausal HF have been devised, but they are not fully available because of the difficulty in producing them. It is thought that hyperactivity of the central α-adrenergic system with a decrease in estrogen participates in the onset of postmenopausal HF. Therefore, in the present study, we examined whether a HF model could be easily produced by administering yohimbine (YOH), a presynaptic α₂-adrenoceptor antagonist which promotes norepinephrine release, to female rats. HF-like symptoms such as a rise in tail skin temperature and a fall in rectal temperature were shown in the rats who received YOH (3 mg/kg) subcutaneously seven days after the ovariectomy (OVX). Such symptoms following YOH administration were observed in sham rats as well, but were much more clearly noted in OVX rats. We next examined the effects of various drugs, which are clinically effective against postmenopausal HF, on HF-like symptoms in YOH-treated OVX rats: clonidine, a presynaptic α₂-adrenoceptor agonist which inhibits norepinephrine release; β-estradiol as an estrogen; and Keishibukuryogan, a Kampo medicine. These drugs inhibited HF-like symptoms in YOH-treated OVX rats. These results suggest that the activity of the α-adrenergic system is enhanced with a decrease in estrogen in OVX rats whereby YOH causes HF-like symptoms more conspicuously than in sham rats. Therefore, it is thought that YOH-treated OVX rats will be a novel and simple model of postmenopausal HF.
潮热（HF）是更年期症状中最常见的现象，在绝经后女性中常伴随雌激素水平下降而出现。潮热的发病机制复杂，目前尚不清楚。迄今为止，已经设计了一些绝经后潮热的动物模型，但由于制作困难，它们并不完全可用。据认为，雌激素减少导致中枢α-肾上腺素能系统功能亢进参与了绝经后潮热的发病。因此，在本研究中，我们研究了给雌性大鼠注射育亨宾（YOH）（一种促进去甲肾上腺素释放的突触前α₂-肾上腺素能受体拮抗剂）是否能轻松建立潮热模型。在卵巢切除（OVX）7天后皮下注射YOH（3mg/kg）的大鼠出现了类似潮热的症状，如尾皮温度升高和直肠温度下降。给予YOH后，假手术大鼠也观察到了此类症状，但在OVX大鼠中更为明显。接下来，我们研究了临床上对绝经后潮热有效的各种药物对YOH处理的OVX大鼠类似潮热症状的影响：可乐定，一种抑制去甲肾上腺素释放的突触前α₂-肾上腺素能受体激动剂；β-雌二醇作为雌激素；以及汉方药物桂枝茯苓丸。这些药物抑制了YOH处理的OVX大鼠的类似潮热症状。这些结果表明，OVX大鼠中雌激素减少会增强α-肾上腺素能系统的活性，从而使YOH比假手术大鼠更明显地引起类似潮热的症状。因此，认为YOH处理的OVX大鼠将是一种新型的、简单的绝经后潮热模型。
