基于胆汁酸-雌激素代谢通路FXR/HNF4α/EST探讨乳腺癌情志病机的科学内涵及四逆散干预研究

情志致病是中医药重大基础理论，历代医家均认为“乳岩乃七情致伤之症”，现代医学也证明慢性心理应激和乳腺癌发生发展密切相关，因此阐释其生物学规律和防治策略对于乳腺癌的治疗及预后具有重要意义。本项目前期研究发现慢性心理应激促进胆汁酸代谢与法尼醇X受体（FXR）激活阻断雌激素硫酸转移酶（EST）的表达，从而诱导雌激素水平上升促进乳腺癌的生长转移。由此设想：四逆散可通过调节胆汁酸-雌激素代谢通路FXR/HNF4α/EST促进雌激素代谢，从而抑制慢性心理应激诱导的乳腺癌转移。本项目拟通过活体荧光示踪、代谢组学、临床标本检测和活性导向追踪分离等技术阐释胆汁酸-雌激素信号通路在慢性心理应激诱导乳腺癌转移中的生物学意义，并揭示四逆散调节胆汁酸代谢抑制乳腺癌发展转移的效靶功能。本项目将丰富中医“情志致病”的科学内涵，为中医药从情志-心理角度防治乳腺癌转移提供新靶点和新策略。

"Emotional pathogenesis" is an important basic theory of traditional Chinese medicine. Physicians believed that "Ruyan is a disease caused by Seven Emotions". The modern medicine has strongly suggested that chronic psychological stress promoted breast tumor development. For this reason, it is important to illustrate its biological mechanisms and treatment strategies for better treatment and prognosis of breast cancer patients. In previous study, we demonstrated chronic psychological stress-facilitated bile acid metabolism, and found that bile acids could activate farnesol X receptor, inhibiting sulfotransferase family 1E member 1 expression. All of these may finally lead to higher levels of estrogen and breast tumor growth and metastasis. Therefore, we assume that Sini formula can promote estrogen metabolism by regulating the bile acid-estrogen metabolism pathway FXR/HNF4α/EST, thereby inhibiting breast cancer metastasis induced by chronic psychological stress. Techniques such as mass spectrometry，fluorescence labeling in vivo，clinical specimen detection and bioactivity tracking and isolation will be applied. Finally, we will explore its molecular mechanism and material basis for regulating bile acid metabolism. This study will explain the connotation of "emotional pathogenesis" on breast cancer, and provide new targets and treatment strategies for inhibiting breast cancer development and metastasis.