海南医科大学学报2026,Vol.32Issue(7):510-518,9.DOI:10.13210/j.cnki.jhmu.20250306.005
小檗碱调控FOXO1/GPX4信号通路对心梗后心衰小鼠的保护作用及机制探讨
Study on the mechanism of berberine inhibiting ferroptosis in heart failure mice by regulating FOXO1/GPX4
摘要
Abstract
Objective:To investigate the mechanism of berberine inhibiting ferroptosis in heart failure mice based on the FOXO1/GPX4 pathway.Methods:H9C2 cells were cultured in vitro and divided into the Control group,the Model group,and the low,medium,and high-dose berberine(BBR-L、BBR-M、BBR-H)groups.A hypoxic cell model of H9C2 was induced using a hypoxic incubator.Cellular apoptosis,reactive oxygen species(ROS),superoxide dismutase(SOD),and malondialdehyde(MDA)content were measured.The expression of FOXO1,GPX4,and SCL7A11 mRNA was detected by PCR.For in vivo ex-periments,a mouse model of heart failure after myocardial infarction was established by coronary ligation and divided into the sham surgery(Sham)group,the Model group,and the berberine(BBR)group(100 mg∙kg-1∙d-1),with 6 mice in each group.Echocardiography and pathological staining such as hematoxylin and eosin(H&E)staining were performed after 4 weeks of treat-ment.The protein levels of FOXO1 and GPX4 were detected by Western blot.Results:In vitro results showed that berberine in-hibited apoptosis in hypoxic H9C2 cells,reduced ROS production,alleviated lipid peroxidation damage,inhibited FOXO1 expres-sion,and increased the expression of GPX4 and SCL7A11 mRNA.In vivo experiments indicated that berberine improved cardiac function in heart failure mice,reduced myocardial cell damage,inhibited myocardial fibrosis,suppressed FOXO1 protein expres-sion,and promoted the expression of the anti-ferroptotic GPX4 protein.Conclusion:Berberine can improve cardiac function in mice with heart failure after myocardial infarction and reduce cell damage caused by hypoxia,potentially through regulating the FOXO1/GPX4 pathway to exert anti-ferroptotic and cardioprotective effects.关键词
小檗碱/心力衰竭/铁死亡/谷胱甘肽过氧化物酶4/叉头盒蛋白O1Key words
Berberine/Heart failure/Ferroptosis/Glutathione peroxidase 4/Forkhead Box Protein O1分类
医药卫生引用本文复制引用
张凌霄,杨成昊,栾玉玲,丁新月,钱俊峰,刘宗军..小檗碱调控FOXO1/GPX4信号通路对心梗后心衰小鼠的保护作用及机制探讨[J].海南医科大学学报,2026,32(7):510-518,9.基金项目
This study was supported by the Shanghai Pu Zhou District Health Commission Priority Discipline Fund Project(2023ysxk01) (2023ysxk01)
Shanghai Putuo District Health System Science and Technology Innovation Fund Project(ptkwws202418) (ptkwws202418)
Shanghai University of Traditional Chinese Medicine Science and Technology Development Fund Project(23KFL083) 上海市普陀区卫健委优势学科基金资助项目(2023ysxk01) (23KFL083)
上海市普陀区卫生健康系统科技创新基金资助项目(ptkw-ws202418) (ptkw-ws202418)
上海中医药大学科技发展基金资助项目(23KFL083) (23KFL083)