【Abstract】Objective To investigate the impact of semaglutide (Sem) on cardiac function, as well as histological and cytological changes following myocardial infarction in mice. Methods Mouse model of myocardial infarction (MI) was induced by ligation of the left anterior descending artery in male KM mice aged 7-8 weeks. Then male KM mice were randomly divided into the sham group, MI group, and Sem treatment group. After four weeks, echocardiography, HE staining, TUNEL staining, and Masson staining were conducted in the four groups. H9c2 rat cardiomyocytes were divided into control group (CON), hypoxia group (Hypoxia), and Sem group. Flow cytometry and Western blotting were utilized to assess the apoptosis of H9c2 cells in the three groups. GraphPad Prism 9.5 was used for statistical analysis. Depending on data type, one-way analysis of variance was used for intergroup comparison, and LSD-t test for pairwise comparison. Results Ultrasonography demonstrated that Sem significantly improved ejection fraction, shortening fraction, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular end-systolic volume and end-diastolic volume when compared with the values of the MI group (P<0.05). Histological observation revealed that Sem treatment reduced the apoptosis rate, abnormal cell morphology rate, and collagen volume fraction of myocardial cells when compared to the MI group (P<0.05). Flow cytometry showed that Sem effectively decreased the apoptosis rate of hypoxic cardiomyocytes, while Western blotting indicated that Sem promoted the expression of anti-apoptotic protein Bcl-2 and reduced the expression of pro-apoptotic proteins Bax and Caspase-3, with statistical significance compared to the hypoxia group (P<0.05). Conclusion Sem can effectively improve cardiac function in mice after MI, reduce ventricular remodeling, and decrease myocardiocyte apoptosis.
