Protective Effect of Tongmai Jiangtang Formula on Hyperglycaemic Cardiomyocytes form Hypoxia/Reoxygenation Induced-injury by Regulating Nrf2-GSH-GPX4-mediated Ferroptosis Pathway
LIU Yuzhe
YE Pan
LIU Ping
LI Xiuqing
Abstract：Objective:To explore the protective effect of Tongmai Jiangtang formula on cardiomyocytes from induced-injury by hypoxia/reoxygenation and hyperglycaemic.Methods:The cardiomyocytes of hyperglycemic mice were divided into normal group,model group,Ferrostatin-1 inhibitor group(Fer-1 inhibitor group,Fer-1 3 μmol/mL),low-dose Tongmai Jiangtang formula group(Tongmai Jiangtang formula 150 mg/mL),medium-dose Tongmai Jiangtang formula group(Tongmai Jiangtang formula 300 mg/mL),and high-dose Tongmai Jiangtang formula group(Tongmai Jiangtang formula 450 mg/mL).Cell counting kit(CCK-8)was used to detect the effect of different doses Tongmai Jiangtang formula on cell viability of injured cardiomyocytes.The contents of glutathione(GSH)and Fe2+were detected by kit.The expressions of ferroptosis signaling pathway related proteins[nuclear factor E2-related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain(Fth1)]were detected by Western Blot.Results:Compared with the normal group,the contents of reactive oxygen species(ROS)and Fe2+increased in the model group,while the contents of GSH and the levels of Nrf2,GPX4 and Fth1 protein decreased,with statistical significance(P＜0.01).Compared with the model group,levels of GSH,Nrf2,GPX4 and Fth1 protein in the different doses Tongmai Jiangtang formula groups and Fer-1 inhibitor group increased,while the contents of ROS and Fe2+decreased,with statistical significance(P＜0.05 or P＜0.01).Conclusion:Tongmai Jiangtang formula showed better protective effect on hyperglycemic cardiomyocytes injured by hypoxia/reoxygenation,decreasing intracellular ROS and Fe2+accumulation,and increasing GSH content and Nrf2,GPX4 and Fth1 protein expression.The mechanism of action might be related to the activation of NRF2-GSH-GPX4 pathway.
Keywords：hyperglycaemic cardiomyocytesTongmai Jiangtang formulaferroptosishypoxia/reoxygenation injurynuclear factor E2 related factor 2-glutathione-glutathione peroxidase 4miceexperimental study
Publication Date：2025-03-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 857-862 )