铁死亡在肝脏疾病中的作用及治疗策略

The role and treatment strategies of ferroptosis in liver diseases

调节性细胞死亡的发现使人类在疾病治疗领域取得了新的突破。作为近十年来新发现的一种调节性细胞死亡,铁死亡的显著特点是细胞内铁离子的异常升高和细胞膜脂质的过氧化破损,形态学特征为线粒体体积缩小、线粒体膜密度增高和线粒体减少或消失。铁死亡的发生机制主要与铁代谢紊乱、脂质代谢异常、氨基酸抗氧化系统失衡和氧化应激等因素相关。由于人体内储存铁离子的主要器官为肝脏,因此深度剖析铁死亡在肝脏疾病中的作用机制非常必要。相关研究表明,铁死亡在不同的肝脏疾病背景下扮演不同的角色,与肝脏疾病的发生过程密切相关,在药物性肝损伤、酒精性脂肪肝、非酒精性脂肪肝、病毒性肝炎、肝纤维化和肝细胞癌等病变过程中都发挥着重要调控作用。本文以铁代谢紊乱、细胞膜脂质过氧化物积累、氨基酸抗氧化系统失衡、线粒体膜电位超极化及其脂质过氧化物积累和氧化应激相关转录因子等方面为切入点,对铁死亡的调控机制、研究现状及其在肝脏相关疾病中的作用进行综述,为铁死亡的深入研究和肝脏疾病的治疗提供新的理论基础和研究思路。

The discovery of regulatory cell death has led to new breakthroughs in the field of disease treatment.As a novel discovered regulatory cell death in the past decade, ferroptosis is characterized by abnormal increase of intracellular iron ions and peroxidative damage of cell membrane lipids, morphological features of mitochondrial volume reduction, increased mitochondrial membrane density, as well as mitochondria decrease or disappear. The mechanism of ferroptosis is mainly associated with factors such as iron metabolism disorder, lipid metabolism abnormality, amino acid antioxidant system imbalance and oxidative stress. Since the liver is the main organ of human body for storing iron ions, it is necessary to deeply investigate the mechanism of ferroptosis in liver diseases.Relevant studies have shown that ferroptosis plays different roles in various liver diseases and is closely related to the process of liver diseases, including drug-induced liver injury, alcoholic fatty liver disease, non-alcoholic fatty liver diseases, viral hepatitis, liver fibrosis and hepatocellular carcinoma. The aim of this review is to link ferroptosis and liver diseases, concentrating on the iron metabolism disorder, accumulation of lipid peroxides in cell membranes,imbalance of amino acid antioxidant system, hyperpolarization of mitochondrial membrane potential and its accumulation of lipid peroxides, oxidative stress-related transcription factors and other aspects. This review summarizes the regulatory mechanism, current situation and the roles of ferroptosis in liver diseases, in order to provide a new theoretical basis and ideas for the in-depth study of ferroptosis and the treatment of liver diseases.