基于Ferroptosis途径探讨Caveolin-1调控脂肪性肝病细胞间串扰机制及痰瘀同治干预作用

肝内细胞间串扰“Crosstalk”是脂肪性肝病的重要调节因素，并与肝纤维化发生密切相关，但其调控机制尚不完全清楚。传统中医药在防治脂肪性肝病领域具有独特优势，痰瘀同治是其关键之法，但其科学内涵仍未完全阐明。基于我们前期研究发现膜蛋白Caveolin-1与脂肪肝发生发展密切相关，其具有抑制氮氧应激调控肝细胞铁死亡（Ferroptosis）的作用机制，而铁死亡又是参与脂肪肝以及肝纤维化发展的共同途径，由此我们考虑Caveolin-1介导铁死亡途径调控细胞间Crosstalk可能是防治脂肪肝纤维化发生的关键途径以及药物靶点，并拟通过高通量斑马鱼以及敲基因小鼠平台，联合体外共培养体系验证，系统分析铁死亡与脂肪肝纤维化发生过程细胞间作用稳态的关系以及Caveolin-1的调控机制，并通过化痰祛瘀中药干预治疗，阐明痰瘀同治对脂肪肝纤维化发生的干预作用及生物内涵，为脂肪性肝病有效预防寻找新的治疗策略。

Hepatic Intercellular crosstalk is an important regulator of fatty liver disease and is closely related to the fibrogenesis. However, its mechanism is not fully understood. Traditional Chinese medicine has the unique advantage in the prevention and treatment of fatty liver diseases, and the simultaneous treatment of phlegm and blood stasis (“tan” and “yu”) is the key way, but its scientific connotation has not yet been clarified. Based on our previous research, we found that the membrane protein caveolin-1 was closely related to the development of fatty liver disease. Caveolin-1 has the ability to inhibit nitrogen and oxygen stress and regulate hepatocytes ferroptosis, which involved in both fatty liver disease and liver fibrosis. Therefore, we consider that caveolin-1 mediate ferroptosis involved in the intercellular crosstalk may be a crucial mechanism for the prevention and treatment of the fibrogenesis in fatty liver disease. We propose to use knockout mice and zebrafish platform combined with in vitro co-culture system, analyze the interaction between ferroptosis and intercellular crosstalk, as well as the regulatory mechanisms of caveolin-1 in the progress of fibrogenesis in fatty liver disease. Meanwhile, we will further verify the intervention effect and biological target of simultaneous treatment of phlegm and blood stasis (“tan” and “yu”) on the fibrogenesis of fatty liver by Traditional Chinese medicine administration. Our finding will provide new strategies for the prevention and treatment of fatty liver diseases.