铁死亡对器官纤维化的影响及中药干预进展

Effect of Ferroptosis on Organ Fibrosis and Intervention Progress of Traditional Chinese Medicine:A Review

纤维化是指组织损伤后修复反应失调,以器官内纤维结缔组织增多和实质细胞减少为主要特征,进行性纤维化可导致组织结构破坏,造成器官功能衰竭。铁死亡是一种新型的程序性细胞死亡方式,由铁依赖性脂质过氧化物累积引起,受铁代谢、铁自噬、氨基酸代谢和脂质代谢等多种途径调节。铁死亡在纤维化病理进程中起着重要作用,参与器官实质细胞损伤、巨噬细胞炎症、氧化应激和肌成纤维细胞转化等多个病理过程。在纤维化级联反应中,肌成纤维细胞在细胞外基质沉积过程中会发生铁死亡,且通过靶向调节铁死亡可有效减轻慢性器官损伤和组织纤维化。现已证实,多种中药及其有效成分可调控器官实质细胞铁死亡发挥抗纤维化作用,显示出良好的研究前景。该文对铁死亡在肝、肺、肾和心脏纤维化病理进程中的作用及相关中药干预进行总结,以期为中药防治纤维化疾病提供新靶点。

Fibrosis refers to the disorder of repair response after tissue damage,which is mainly characterized by the increase of fibrous connective tissue and the decrease of parenchymal cells in organs.Progressive fibrosis can lead to the destruction of tissue structure and organ failure.Ferroptosis is a new type of programmed cell death,which is caused by the accumulation of iron dependent lipid peroxides and regulated by iron metabolism,iron autophagy,amino acid metabolism and lipid metabolism.Ferroptosis plays an important role in the pathological process of fibrosis,participating in many pathological processes such as organ parenchymal cell injury,macrophage inflammation,oxidative stress and myofibroblast transformation.Studies have shown that ferroptosis occurs in myofibroblasts during extracellular matrix deposition in the fibrous cascade reaction,and the targeted regulation of ferroptosis can effectively reduce chronic organ injury and tissue fibrosis.It has been confirmed that a variety of traditional Chinese medicine and its active components can regulate the ferroptosis parenchyma cells of organs and play an anti-fibrosis effect,showing a good research prospect.This article summarizes the role of ferroptosis in the pathological process of liver,lung,kidney and heart fibrosis and the intervention of related Chinese medicine,in order to provide a new target for Chinese medicine to prevent and treat fibrosis.