GPX4在非酒精性脂肪肝病中的作用机制及中药提取物干预研究
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1广西中医药大学瑞康临床医学院,2第一临床医学院,广西 南宁 530001 ; 3.广西中医药大学基础医学院,广西 南宁 530200

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广西自然科学基金青年科学基金(2020GXNSFBA159043);广西中医药大学2019—2021年广西一流学科建设开放课题(2019XK083);广西自治区级大学生创新创业训练计划(S202310600074);广西中医药大学科研训练课题(2023DXS06)


The mechanistic role of GPX4 in nonalcoholic fatty liver disease and intervention studies using traditional Chinese medicine extracts
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1Ruikang Clinical Medical College,2the First School of Clinical Medicine,Guangxi University of Chinese Medicine,Nanning 530001 ; 3.School of Basic Medical Science,Guangxi University of Chinese Medicine,Nanning 530200 ,China

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    摘要:

    非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是目前全球最常见的慢性肝病,严重威胁人类健康, 但其发病机制尚不完全清楚,调节性细胞死亡的研究为疾病治疗提供了新思路。铁死亡是一种依赖铁的非凋亡细胞死亡方式,铁代谢紊乱、氧化还原失衡和脂质过氧化积累均可导致铁死亡。由于肝脏在铁储存和脂质代谢中起关键作用,近年来的研究表明,铁死亡与NAFLD紧密相关。细胞内脂质异常堆积引起氧化还原失衡,可能成为脂质代谢紊乱的一个重要原因,因此, 抑制铁死亡成为NAFLD的潜在治疗新策略。谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)是铁死亡的重要调控蛋白,能够与谷胱甘肽结合,降解活性氧和过氧化氢,从而减少脂质过氧化所造成的损伤。目前研究发现,黄芪、绿茶、黄连等中药的活性成分通过多个靶点可调节GPX4,从而影响NAFLD。文章探讨了铁死亡途径中GPX4的作用机制,并寻找通过GPX4 治疗NAFLD的中药提取物。

    Abstract:

    Non - alcoholic fatty liver disease(NAFLD)is currently the most prevalent chronic liver disease worldwide,posing a significant threat to human health;however,its pathogenesis remains incompletely understood. Research on regulatory cell death has opened new avenues for disease treatment. Among these,ferroptosis is a form of iron-dependent non-apoptotic cell death,which can be triggered by disturbances in iron metabolism,redox imbalance,and the accumulation of lipid peroxides. Given the liver's critical role in iron storage and lipid metabolism,recent studies have established a close association between ferroptosis and NAFLD. Abnormal lipid accumulation within cells can lead to redox imbalance,which may be a key factor contributing to lipid metabolism disorders. Consequently,inhibiting ferroptosis has emerged as a potential therapeutic strategy for NAFLD. Glutathione peroxidase 4(GPX4)is a pivotal regulatory protein in ferroptosis,capable of binding glutathione(GSH)to degrade reactive oxygen species(ROS)and hydrogen peroxide,thereby mitigating lipid peroxidation damage. Current research indicates that active components from traditional Chinese medicines,such as astragalus membranaceus,green tea,and coptis,can modulate GPX4 through multiple targets,thereby influencing NAFLD. This review explores the mechanisms by which GPX4 operates within the ferroptosis pathway and identifies herbal extracts that may offer therapeutic benefits for NAFLD through GPX4 regulation.

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马晓月,杨宇帆,陈永欣. GPX4在非酒精性脂肪肝病中的作用机制及中药提取物干预研究[J].南京医科大学学报(自然科学版),2025,(11):1678-1688

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  • 收稿日期:2025-01-22
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  • 在线发布日期: 2025-11-12
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