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Six weeks of aerobic exercise significantly upregulated the expression of fibroblast growth factor 21 (FGF21), FGFR1, and peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1) in the paraventricular nucleus of mice with myocardial ischemia/reperfusion injury, increased the phosphorylated AMP-activated protein kinase alpha (p-AMPK)/AMPK ratio, upregulated the expression of SOD1, SOD2, and sestrin 2 (SESN2), reduced ROS levels, downregulated the expression of TFR1 and FTH, upregulated the expression of FPN1, suppressed neuronal oxidative stress and ferroptosis, thereby ameliorating neuronal injury in mice with myocardial ischemia/reperfusion injury