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OA

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.