The Mechanism of Total Flavonoids of Astragalus on STAT3 Protein Expression and Ferroptosis in Protecting Myocardial Ischemia-reperfusion Injury
XU Huanjie
HUANG Yingyuan
LIN Jie
Abstract：Objective:To explore the effects of total flavonoids of Astragalus on the expression of signal transducer and activator of transcription 3(STAT3)and the level of ferroptosis in myocardial tissue of rats with myocardial ischemia-reperfusion(I/R),and the possible protective mechanism.Methods:Seventy rats were divided into sham operation group,I/R group,low-dose total flavonoids of Astragalus group,medium-dose total flavonoids of Astragalus group,high-dose total flavonoids of Astragalus group,phosphorylated STAT3(p-STAT3)blocker(Stattic)group,and ferroptosis inducer(Erastin)group,with 10 rats in each group.The hemodynamic indicators of rats[left ventricular systolic blood pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum rate of increase in left ventricular pressure(+dp/dtmax),and maximum rate of decrease in left ventricular pressure(-dp/dtmax)]were determined by BL-420F.The histopathological changes of myocardial tissue were observed by hematoxylin-eosin(HE)staining.The kit was used to detect the contents of creatine kinase(CK),lactate dehydrogenase(LDH),and aspartate aminotransferase(AST)in rat serum.The protein levels of STAT3,p-STAT3,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and acyl coenzyme A synthetase long chain family member 4(ACSL4)in myocardial tissue were detected by Western Blot.The kit was used to detect the contents of GSH,Fe2+,and reactive oxygen species(ROS)in serum of rats.Results:Compared with the sham operation group,the LVSP and+dp/dtmax,-dp/dtmax of rats in the I/R group decreased(P＜0.01),and the contents of LVEDP,CK,LDH and AST increased(P＜0.01).The myocardial tissue structure of rats exhibited marked damage,with numerous myocardial fibres rupture and inflammatory cell infiltration was observed.The ratio of STAT3/p-STAT3 in myocardial tissue of rats,the expression of ACSL4 protein,and the contents of ROS and Fe2+ increased(P＜0.05),while the contents of SLC7A11,GPX4 protein,and serum GSH decreased(P＜0.05).Compared with the I/R group,the LVSP and+dp/dtmax,-dp/dtmax of rats in the different dose total flavonoids of Astragalus groups increased,while the LVEDP and the contents of serum CK,LDH,and AST decreased(P＜0.05 or P＜0.01).In the later experiments,the high-dose total flavonoids of Astragalus group was selected as the protection group for the study.Compared with the I/R group,the ratio of STAT3/p-STAT3,the expression of ACSL4 protein,and the contents of ROS and Fe2+in the myocardial tissue of rats in the high-dose total flavonoids of Astragalus group decreased(P＜0.05).The protein levels of SLC7A11 and GPX4 and the content of serum GSH increased(P＜0.05),and the changes of each index in the Stattic group were consistent with those in the high-dose total flavonoids of Astragalus group(P＜0.05).Compared with the high-dose total flavonoids of Astragalus group,the contents of CK,LDH,and AST in the Erastin group of rats increased(P＜0.01).Conclusion:The total flavonoids of Astragalus might improve the cardiac function and structure in I/R rats by inhibiting the phosphorylation of STAT3 and the level of ferroptosis.
Keywords：myocardial ischemia-reperfusiontotal flavonoids of Astragalussignal transduction and transcription activator 3ferroptosisratsexperimental study
Publication Date：2025-11-25
Online Publishing Date：2025-12-05(First online date of this platform, not the publication date of the document)
Pages：7( 3416-3422 )