铁死亡在肝纤维化中的作用及中医药干预的研究进展

The role of ferroptosis in liver fibrosis and the progress of traditional Chinese medicine intervention

关键词:  肝纤维化  铁死亡  中医药  研究进展

Key words:  liver fibrosis  ferroptosis  traditional Chinese medicine  research progress

摘要:

肝纤维化是各种慢性肝病最常见的病理特征，可发展至肝硬化、肝癌，及时干预阻断疾病进程至关重要。铁死亡作为近些年新发现的细胞死亡形式，可以通过铁过载和脂质过氧化诱导肝纤维化的发生发展，也可以通过诱导肝星状细胞铁死亡限制产生纤维化瘢痕细胞的扩张，减轻肝纤维化反应的损伤。因此，精准的调控铁死亡是治疗肝纤维化的关键环节。中医药治疗肝纤维化具有独特优势，研究表明黄酮类、内酯类、生物碱类、三萜类、蒽醌类和有机金属化合物等中药活性成分和复方可通过BRD7-P53-SLC7A11、SOCS1/P53/SLC7A11、Keap-1/Nrf2、ROCK1/ATF3等信号通路；调控GPX4、SLC7A11、IRP2、NCOA4、HO-1等靶点活性；或促进铁蛋白自噬等途径影响细胞铁代谢和脂质过氧化过程，进而促进活化的肝星状细胞铁死亡或抑制正常肝细胞铁死亡发挥肝纤维化治疗作用。本文对铁死亡在肝纤维化中的作用以及中医药调节铁死亡干预肝纤维化的研究进展进行综述，为中医药治疗肝纤维化提供新的研究方向。

Abstract:

Liver fibrosis is the most common pathological feature of various chronic liver diseases, which can progress to cirrhosis and hepatocellular carcinoma, and it is crucial to intervene in time to block the disease process. Ferroptosis, as a newly discovered form of cell death in recent years, can induce the development of liver fibrosis through iron overload and lipid peroxidation, and it can also mitigate the damage of hepatic fibrotic response by inducing ferroptosis in hepatic stellate cells to limit the expansion of fibrotic scar-producing cells. Therefore, precise regulation of ferroptosis is a key component in the treatment of liver fibrosis. Traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis. Studies have shown that TCM active ingredients such as flavonoids, lactones, alkaloids, triterpenoids, anthraquinones, and organometallic compounds can be used to pass through the signaling pathways such as BRD7-P53-SLC7A11, SOCS1/P53/SLC7A11, Keap-1/Nrf2, and ROCK1/ATF3; and to regulate the activities of the targets such as GPX4, SLC7A11, IRP2, NCOA4, HO-1, and so on; and to affect the cellular iron metabolism and lipid peroxidation process by pathways such as promoting ferritin autophagy, thereby preventing and treating liver fibrosis. This paper provides a review on the role of ferroptosis in liver fibrosis and the research progress of TCM in regulating ferroptosis to intervene in liver fibrosis, so as to provide a new research direction for the treatment of hepatic fibrosis by TCM.