摘要Heart failure(HF)is a major contributor to global morbidity and mortality,with myocardial infarction(MI)-induced HF accounting for a substantial proportion of cases.Although Yangx-inshi Tablet(YXS)is clinically used,the mechanisms by which it alleviates HF remain unclear.To elucidate the protective mechanisms of YXS in post-MI HF.An MI-induced HF model was established in male Sprague-Dawley rats,and cardiac function,exercise endurance,hemody-namics,serum biochemical indices,and pathological damage were assessed.To investigate the underlying mechanisms,metabolomics,quantitative polymerase chain reaction(qPCR),ribonucleic acid sequencing(RNA-seq),Western blot,immunofluorescence,chromatin-im-munoprecipitation(ChIP)-qPCR,and single-cell RNA-seq were employed.The components of YXS were analyzed via molecular docking,and their biological activity was validated in cell-based assays.YXS improved cardiac function and exercise endurance,enhanced hemodynam-ic parameters,reduced inflammatory cell infiltration,and decreased collagen fiber deposition in vivo.In vitro,YXS regulated mitochondrial energy metabolism and protected against oxygen-glucose deprivation(OGD)-induced cardiomyocyte injury.Notably,YXS ameliorated post-MI HF by inhibiting forkhead box O1(FOXO1)/pyruvate dehydrogenase kinase 4(PDK4)signal-ing,thereby promoting the tricarboxylic acid(TCA)cycle and increasing adenosine 5'-triphos-phate(ATP)levels to restore energy metabolism both in vivo and in vitro.Senkyunolide H,apigenin,astragaloside Ⅳ,and astragaloside Ⅶ were identified as active constituents of YXS using an OGD-induced H9c2 cell injury model.These findings indicate that YXS exerts cardi-oprotective effects in a rat model of post-MI HF.Mechanistically,YXS inhibits FOXO1/PDK4 signaling,enhances TCA cycle activity,and elevates ATP production to improve cardiac en-ergy metabolism and restore energy homeostasis.