Study on the protective effect of DanShenTongLuo-detoxification decoction modulating Nrf2-GPX4-mediated ferroptosis pathway on myocardial ischaemia/reperfusion injury rats
Objective To explore the protective effect of DanShenTongLuo-detoxification decoction on myocardial ischaemia/reperfu-sion(I/R)injury in rats based on the nuclear factor E2-related factor 2(Nrf2)-glutathione peroxidase 4(GPX4)-mediated ferrop-tosis pathway.Methods SD rats were randomly divided into control group,sham-operated group,model group.Methods(I/R),tradi-tional Chinese medicine group(I/R+DanShenTongLuo-detoxification decoction),and Nrf2 inhibitor+traditional Chinese medicine group(I/R+ML385+DanShenTongLuo-detoxification decoction),with 8 rats in each group.Transmission electron microscopy was used to observe the ultrastructure of myocardium;Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tropo-nin I(cTnI),troponin T(cTnT),and reactive oxygen species(ROS)in myocardial tissues;Biochemical methods were used to detect the activities of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione(GSH),and Fe2*content in myocardial tissues;Western blot detected the protein levels of GPX4 and Nrf2 in myocardial tissues.Results Compared with the control group or the sham-operated group,the mitochondrial cristae of rat cardiomyocytes in the model group were broken,reduced or even disappeared,and the myocardial tissue levels of cTnI and cTnT,ROS,MDA,and Fe2+were elevated(P＜0.05),and the activities of SOD,GSH content,and the expression of Nrf2 and GPX4 proteins were reduced(P＜0.05);Compared with the model group,mitochondrial damage in rat cardiomyocytes was significantly improved in the traditional Chinese medicine group and the Nrf2 inhibitor+traditional Chinese medicine group,and the myocardial tissue cTnI and cTnT levels,ROS,MDA,and Fe2+contents were reduced(P＜0.05),and SOD activity,GSH content,as well as the protein expression of GPX4 and Nrf2 were elevated(P＜0.05);Compared with the traditional Chinese medicine group In the Nrf2 inhibitor+Chinese medicine group,mitochondrial damage in rat cardiomyocytes was aggravated,and myocar-dial tissue cTnI and cTnT levels,ROS,MDA,and Fe2+contents were elevated,and SOD activity,GSH content,as well as GPX4 and Nrf2 protein expression were decreased(P＜0.05).Conclusion DanShenTongLuo-detoxification decoction may attenuate myocardial I/R injury by inhibiting ferroptosis,and its mechanism of action may be related to the activation of the Nrf2-GPX4 pathway.
万方数据
维普
