Objective To investigate the effect and mechanism of notoginsenoside R₁ (NGR1) on cardiac remodeling after myocardial ischemia-reperfusion injury (MIRI) in mice. Methods A model of cardiac remodeling after myocardial ischemia-reperfusion injury (MIRI) was established by ligating the anterior descending branch of the coronary artery in mice. After three weeks of intervention with NGR1, the cardiac index and heart weight/tibia length of mice were measured. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured using a small animal ultrasound instrument. The cross-sectional area of myocardial cells was calculated by wheat germ agglutinin (WGA) fluorescence staining. The collagen volume fraction (CVF) of heart was calculated by Masson staining. The protein expressions of collagen I, collagen III, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transferrin receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in myocardial tissue were detected by Western blotting. The possible mechanism of NGR1 inhibiting cardiac remodeling after MIRI was preliminarily explored through network pharmacology. The contents of iron ions (Fe²⁺) and lipid peroxide (LPO) in myocardial tissue were detected using kits. The damage of myocardial mitochondria was observed by transmission electron microscopy. Results Compared with sham group, cardiac index, heart weight/tibia length, LVEDV, LVESV and CVF of mice in model group were significantly increased (P < 0.05, 0.01), protein expressions of collagen I, collagen III, ANP, BNP, TFR1 and ACSL4 in myocardial tissue were significantly increased (P < 0.01), contents of Fe²⁺ and LPO were significantly increased (P < 0.05, 0.01), mitochondrial membrane density was increased and cristae was decreased, SLC7A11 and GPX4 protein expressions were significantly decreased (P < 0.01). Compared with model group, cardiac index, heart weight/tibia length, LVEDV, LVESV and CVF of mice in NGR1 administration groups were significantly decreased (P < 0.05, 0.01), protein expressions of collagen I, collagen III, ANP, BNP, TFR1 and ACSL4 were significantly decreased (P < 0.05, 0.01), contents of Fe²⁺ and LPO were significantly decreased (P < 0.05, 0.01), mitochondrial damage was improved, SLC7A11 and GPX4 protein expressions were significantly increased (P < 0.05, 0.01). Conclusion NGR1 could significantly improve cardiac remodeling in mice after MIRI, and its mechanism may be related to the activation of SLC7A11/GPX4 pathway to inhibit ferroptosis of cardiomyocytes.

notoginsenoside R₁  /  SLC7A11/GPX4 pathway  /  ferroptosis  /  myocardial ischemia-reperfusion injury  /  cardiac remodeling