黄皮酰胺抑制Ferroptosis保护酒精性肝损伤的作用机制研究

Ferroptosis是近年来发现的新型细胞死亡方式。开发具有ferroptosis抑制活性药物是当前国际热点。以往研究认为酒精诱导细胞死亡方式主要是坏死和凋亡，本项目前期研究首次发现，酒精诱导肝细胞死亡中也存在ferroptosis现象，为研究保护酒精肝药物提供了新思路。我们在大量天然产物的ferroptosis活性抑制筛选过程中发现，来自中药黄皮中的活性成分黄皮酰胺能明显抑制ferroptosis保护酒精性肝损伤，机制可能是与激活Keap-Nrf2通路相关。本项目的科学问题是：黄皮酰胺保护酒精诱导肝ferroptosis生物学机制，为开发新型的保护酒精性肝损伤的药物提供基础数据。本项目的科学设想是：建立体内外酒精诱导肝ferroptosis模型，确认黄皮酰胺的药效作用和对ferroptosis的抑制作用；采用基因敲除等技术探讨Keap1-Nrf2通路在其中的调节机制。

Ferroptosis is a recently new form of programmed oxidative cell death. Inhibition of ferroptosis is pilot issues of new drug research in the world. Our study identify the novel mechanism that contributes to alcohol liver injury through the induction of ferroptosis, a distinctive form of necrosis and apoptosis. We continually applied to screen active natural products through models of ferroptosis. Clausenamide, which are active ingredients separated from the clausena lansium, can significantly protect alcoholic liver injury through inhibiting ferroptosis. The mechanism was proposed to be related to activate of the Keap1-Nrf2 pathway. But this hypothesis still needs to be proven. Therefore, our research intends to confirm clausenamide have protective effects in alcohol-induced liver injury in vitro and in vivo, which is through inhibiting ferroptosis. We also intend to investigate its regulatory mechanism of Keap1-Nrf2 pathway in ferroptosis by gene knockout technology.