Objective To study the protective effects of dapagliflozin on myocardial injury after myocardial infarction in experimental pigs, and explore the action mechanism of the Bax/Bcl-2/Caspase-3 signaling pathway.

Methods Fifteen experimental white pigs (regardless of gender) were randomly divided into the sham operation group (normal group), myocardial infarction group (model group) and dapagliflozin group (drug group), with 5 pigs in each group. Hematoxylin-eosin staining was used to observe the pathological changes of myocardial tissue of pigs. The mRNA expression levels of transforming growth factor (TGF)-β1, fibroblast growth factor 9 (FGF9), plaque adhesion protein 1 (FN1), and galactoside-binding lectin 3 (LGALS3) in each group were detected by real-time fluorescence quantitative PCR. The contents of interleukin (IL) -1β, IL-6 and tumor necrosis factor -α (TNF-α) in the myocardium of each group were detected by enzyme-linked immunosorbent assay (ELISA). TUNEL staining was used to detect the apoptotic cells in the myocardium of each group. Western blotting was used to detect the expression levels of Bax, Bcl-2, apoptosis-associated protease (Caspase) -3 and caspase-9 proteins in the cardiac tissues of each group.

Results Compared with the normal group, the myocardial tissue in the model group was loose and edematous, with disordered arrangement of myocardial cells and unclear boundaries, accompanied by inflammatory cell infiltration. Collagen deposition could be seen in the infarction area, which was replaced by fibrous tissue. The expression levels of IL-1β, IL-6 and TNF-α increased (P ＜ 0.01), and the mRNA expression levels of fibrosis-related genes TGF-β1, FGF9, FN1 and LGALS3 also increased (P ＜ 0.05). The apoptotic cells increased significantly, and the protein expression levels of Bax, Caspase-3 and Caspase-9 increased (P ＜ 0.01), while the protein expression of Bcl-2 decreased significantly (P ＜ 0.01). After the intervention in the drug group, the apoptosis and fibrosis of myocardial cells could be significantly improved, and the relative expression levels of TGF-β1, FGF9, FN1, and LGALS3 mRNA and expressions of IL-1β, IL-6, and TNF-α could be reduced (P ＜ 0.01). The expression of apoptosis-related proteins Bax, Caspase-3, and Caspase-9 were inhibited (P ＜ 0.01), and the expression level of Bcl-2 protein increased (P ＜ 0.01).

Conclusions Dapagliflozin inhibits myocardial cell apoptosis and fibrosis and has a protective effect on myocardial injury. Its mechanism of action is related to reducing the release of inflammatory factors IL-1β, IL-6, and TNF-α, and inhibiting the Bax/Bcl-2/Caspase-3 apoptotic signaling pathway.