葫芦素E介导FXR与STAT3信号通路交叉对话改善肝纤维化的机制研究

肝纤维化是多种慢性肝病向肝硬化发展的共同病理基础，通过干扰促纤维化细胞因子信号通路或控制炎症反应一直是抗肝纤维化的研究重点。目前肝纤维化临床治疗缺乏安全有效的药物。FXR在胆汁酸、肝内脂类新陈代谢以及炎症介质调控中发挥重要作用，其配体与肝纤维化相关细胞和分子 的关系研究为肝纤维化治疗提供了新的思路。FXR活化细胞中STAT3参与细胞的增殖、分化、凋亡以及免疫调节，同时FXR影响STAT3负反馈因子SOCS3，与肝纤维化有极其密切的联系。因此提出FXR和STAT3信号通路交叉对话是治疗肝纤维化的重要靶点。葫芦素E是十字花科或葫芦科植物提取的一种四环三萜类物质，前期研究发现葫芦素E可诱导活化肝星状细胞凋亡，具有显著抑制肝纤维化进程的作用。本研究基于FXR和STAT3信号通路交叉对话作为肝纤维化潜在治疗靶点，探讨葫芦素E改善或逆转肝纤维化的作用机制。

Hepatic fibrosis is the common pathological basis of various chronic liver diseases developing to liver cirrhosis. Interfering profibrotic cytokines and controlling inflammation are constant the research priorities of anti-hepatic fibrosis, while safe and effective medicines are still deficient in clinic. FXR plays an important role in the regulation of bile acid, Intrahepatic lipid metabolism and inflammation mediators. Researches between ligand of FXR and correlated cells and molecules of hepatic fibrosis present the new way for the treatment. FXR activates STAT3 to regulate cell proliferation, cell differentiation, apoptosis and immunological regulation. FXR affects SOCS3, a degenerative feedback factor of STAT3, and presents an extremely close relationship with hepatic fibrosis. Therefore, FXR-STAT3 crosstalk could be regared as the potencial targets for treatment of hepatic fibrosis. Cucurbitacin E is a triterpenoids isolated from Cruciferae or Cucurbitaceae. Previous study found cucurbitacin E could induce apoptosis of activated HSCs and presented a significant effect for treating hepatic fibrosis. The study focuses on regulation of cucurbitacin E on hepatic fibrosis via FXR-STAT3 crosstalk in vivo and in vitro.