Objective To investigate the impact of cardiomyocyte ferroptosis on acute myocardial infarction(AMI)and its relationship with the expression of long non-coding RNA(lncRNA)GAS5.Methods An AMI model was established in eighteen male SD rats(6-8 weeks old),and then the subjected rats were randomly divided into blank control group,sham operation group,and model group,6 animals in each group.In 2 weeks after surgery,echocardiography was used to evaluate heart function,and TTC staining,HE staining and TUNEL staining were employed re-spectively to observe myocardial infarct area,histopathological changes of myocardial tissues and apoptosis in cardiomyocytes.Serum Fe2+concentration was measured with an iron ion detection kit.The expression levels of lncRNA GAS5,nuclear factor erythroid-derived 2-like 2(Nrf2),and glutathione peroxidase 4(GPX4)in myocardial tissues were detected with QT-PCR.Linear corre-lation analysis was performed to investigate the relationship between the expression of lncRNA GAS5,Nrf2 and GPX4 with Fe2+concentration.Western blotting was conducted for the protein levels of ferroptosis-related proteins,glutathione peroxidase 4(GPX4),nuclear factor erythroid-derived 2-like 2(Nrf2),glucose-regulated protein 78(GRP78),and cysteinyl aspartate specific proteinase 12(Caspase-12)in myocardial tissues.Results Western blotting revealed obvious in-creases in the protein levels of ferroptosis related proteins GRP78(1.11±0.13 vs 0.51±0.08,P＜0.01)and Caspase-12(1.23±0.05 vs 0.92±0.07,P＜0.05)and a decrease in those of ferroptosis inhibitor GPX4(0.27±0.11 vs 0.68±0.10,P＜0.01)and Nrf2(0.30±0.12 vs 0.58±0.04,P＜0.05)in the model group than the sham operation group.Additionally,QT-PCR showed that the mRNA levels of GPX4 and Nrf2 were notably lower,indicating cardiomyocyte ferroptosis,while that of lncRNA GAS5 was remarkably higher in the myocardial tissues of the model group than the sham operation group(P＜0.01).What's more,the expression of lncRNA GAS5 had a positive correlation with serum Fe2+concentration(P＜0.05).Conclusion AMI is closely associated with cardiomyocyte ferroptosis.lncRNA GAS5 is involved in the regulation of ferroptosis by Nrf2/GPX4 signaling pathway,which thus mediating the occurrence of heart failure after AMI.