中文摘要：

目的：前期研究发现围绝经期综合征（PPS）肝郁大鼠海马组织雌激素受体基因ERα/ERβ的比例显著下调。本研究将从表观遗传学角度进一步探讨雌激素受体基因启动子区的甲基化状态与ERα/ERβ比例发生改变的关系。方法：将13月龄雌性自然衰老SD大鼠随机分为PPS对照组、PPS模型组,另取3月龄成年雌性SD大鼠做青年对照组。运用重亚硫酸氢盐测序（BSP）法分析不同组别大鼠海马组织ERα和ERβ基因的甲基化状态。结果：PPS对照组及青年对照组ERα、ERβ基因的Cp G位点呈低甲基化状态,无显著性差异;PPS模型组ERα基因的甲基化位点及其甲基化率均显著增加（P〈0.01）,而ERβ基因启动子则几乎不发生甲基化。结论：PPS模型组ERα基因甲基化水平升高可能是导致PPS肝郁海马组织ERα/ERβ的表达比例下调的重要原因之一。

英文摘要：

Objective： Previous study demonstrated that the ratio of hippocampal ERα and ERβ m RNA（ERα/ERβ ratio） significantly decreased in the rat model of perimenopausal syndrome（PPS） with liver-qi stagnation syndrome. Therefore, this study explored the estrogen receptors（ER） gene methylation of promoter regions to explain why the ERα/ERβ ratio appeared to decrease. Methods： 13-month-old female naturally aged SD rats were randomly divided into the PPS control group and PPS model group, and 3-month-old female SD rats were subjected as the young control group. Bisulfite sequencing PCR（BSP） was used to analyze the methylation of ER gene in the rat hippocampus. Results： The ERα and ERβ genes methylation of Cp G promoter regions were attenuated in both of the young control group and PPS control group, with no significant difference. The ERα gene methylation of promoter regions as well as its methylation rate was significantly increased in PPS model group when compared with the control group（P〈0.01）. But, the ERβ gene methylation of promoter regions was not observed in this study. Conclusion： PPS enhanced the methylation level of ERα gene may be one of the most important factors for the down-regulation of ERα/ERβratio in hippocampus of rat model of perimenopausal syndrome with stagnation of the liver-qi syndrome.