中药方剂是中医临床治疗的主要手段，应用现代药理学实验方法从整体、细胞、分子水平系统、深入地阐释方剂的作用靶点和分子通路，探究其最佳配比规律是方剂研究的焦点和热点问题。四物汤在临床治疗妇科疾病、补血调经方面有着长期、广泛的应用和确凿的疗效，但从靶向不同亚型雌激素受体及其信号传导分子通路入手系统探究其配比规律和作用机理的研究尚未见报道。本课题利用整体动物结合体外细胞培养实验，从四物汤在子宫、心血管、骨骼等靶部位发挥作用的核心靶点——雌激素受体三种亚型：ERα、ERβ和GPER对下游雌激素效应基因表达的介导和调控途径入手，结合基因沉默、质粒转染等技术分析四物汤以下游PI3K/AKT及MAPK/ERK途径为主要分子通路，影响雌激素靶向基因表达的雌激素样效应及其分子机理；并揭示不同ER亚型在介导四物汤发挥疗效过程中的相互关系。研究结果将为四物汤在妇科临床的合理、有效用药提供重要理论基础和实验依据。

Chinese medicinal formulae plays important roles in clinical treatment by TCM. In order to reveal the target point and molecular pathway of the decoction and explore its compatibility law which are key problems and hot issues need to be solved in TCM research, modern pharmacological techniques majoring at integral, cellular and molecular levels will be employed in the research. Siwu decoction has been applied widely and effectively in treating gynecological disease by nourishing blood and regulating menstruation. But till now there has been no systematic report on the pharmacological mechanism and compatibility law of Siwu targeting specific subtype of ER and its related signal transductive molecular pathway. In the current research, the above issue will be studied by both in vitro and in vivo experiments, mainly by focusing on the inductive and regulative function of the three core target points of Siwu including ERα, ERβ and GPER towards downstream estrogen effective gene expression in the target organs, such as uterus, cardiovasalar system and bone. Techniques including gene silence and plasmid transfection will be employed to analyze the estrogenic function and its molecular mechanism of Siwu by detecting expression level of the estrogen targeting genes via downstream PI3K/AKT and MAPK/ERK molecular pathway. The interrelation among the pathway via different estrogen receptor subtypes in realizing Siwu's therapeutic effects will also be analyzed. The results will contribute to provide important theoretic basis and experimental evidence for the rational and effective medication in clinical application of Siwu decoction.