雌激素受体（ER）表达低下是更年期动脉粥样硬化（AS）发病的基础，而ER基因甲基化是ER表达下调的关键。前期研究发现更年期AS模型ER表达下调，六味地黄方可以通过增加ER表达来防治更年期AS。因此我们提出“六味地黄方调节ER基因甲基化，上调ER表达可能是其滋补肾阴作用的关键，也是其干预更年期AS发生的重要机制”的假说。我们将复制ApoE-/-小鼠更年期AS和相关细胞模型，利用BSP、RT-PCR、慢病毒转染、Western bloting等分子生物学技术，选取不同阶段的病变组织及细胞，从ER甲基化及甲基化位点的筛选、甲基供体相关产物（SAM、SAH）及相关酶等、甲基转移酶（DNMTs）活性等方面，来论证上述假说；并利用ER荧光标记细胞株研究其物质基础，最终从表观遗传学的角度阐述滋补肾阴的六味地黄方调节ER基因甲基化，防治更年期心血管疾病的作用机理，为其临床用于预防更年期疾病提供科学依据。

The low expression of estrogen receptor(ER) is the basic pathogenesis of menopausal atherosclerosis (AS). While the methylation of ER genes is the critical factor to the down-regulation of ER expression. According to previous research, we found the expression of ER was down-regulated in menopausal AS models. Liuwei Dihuang Formula was able to prevent AS by increasing the expression of ER. As a result, we put forward the hypothesis that regulating ER methylation, improving ER expression are promising to be the crucial point of Liuwei Dihuang Formula in nourishing kidney-yin, and also the essential mechanism for the intervention of menopausal AS. Our laboratory will replicate AS models on ApoE-/- mice and linked cell models, apply molecular biology techniques like BSP, RT-PCR, Lentivirus transfection and Western blotting. We will select pathological tissues and cells in different stages to argue the hypothesis from the aspects of ER methylation and screenings of methylation sites, relevant productions of methy donators(SAM,SAH) and related enzymes, DNA methytransferases(DNMTs) activity. Meanwhile, we will study the material base by using ER fluorescence labeled cell lines. At last, we hope to illustrate the mechanism of Liuwei Dihuang Formula regulating ER methylation, preventing menopausal cardiovascular diseases in order to provide scientific evidences for applying Liuwei Dihuang Formula to prevent menopausal disorders clinically from the view of epigenetics.