Abstract：Purpose To investigate the improvement effect of dapagliflozin with heart failure based on SIRT1/AMPK pathway. Methods Animal TAC models were developed in C57BL/6J mice and divided into sham, sham+DAPA, TAC, and TAC+DAPA groups. Gravimetric and histological analysis of organ size and weight, HE staining, WGA staining, Masson, Sirius Red staining, DHE staining and TUNEL assay to analyze histopathology, cardiomyocyte size, collagen fibers, ROS production and apoptosis, qRT- The expressions of atrial natriuretic factor (Nppa), brain natriuretic peptide (Nppb), myosin heavy chain 7(Myh7), TGF-β1 and SIRT1/AMPK signaling pathway were detected by PCR and western blotting. Results CHW/TL, HW/BW and HW/LW were significantly reduced in DAPA TAC mice compared with sham operation group. As assessed by WGA staining, the mean cross-section area of cardiocytes in TAC mice was larger. Increases in Nppa, Nppb, and Myh7, in addition to high levels of ANP and β-MHC in TAC mice, decreased mean cardiomyocyte cross-sectional area was observed in DAPA-administered TAC mice. mRNA and protein levels of markers of cardiac hypertrophy were significantly reduced. Masson and Sirius red were used to examine the degree of myocardial fibrosis. Compared with the sham operation group, the myocardial fibrosis area of TAC mice was significantly increased, the mRNA and protein levels of TGF-β1 in TAC group were increased, and the myocardial ROS levels of TAC mice were higher. TUNEL staining showed that the apoptosis rate of cardiomyocytes in TAC group was significantly increased, and the expression of SIRT1/AMPK pathway was decreased, but DAPA had the opposite effect, the difference was statistically significant. ompared with the sham-operated group, HW/TL, HW/BW and HW/LW were significantly reduced in TAC mice with DAPA, and the mean cross-sectional area of cardiomyocytes in TAC mice was large, Nppa, Nppb and Myh7 as assessed by WGA staining In addition, TAC mice had high levels of ANP and β-MHC, and a reduction in mean cardiomyocyte cross-sectional area and significantly lower mRNA and protein levels of cardiac hypertrophy markers were observed in DAPA-administered TAC mice. Masson and Sirius Red examined the degree of myocardial fibrosis. Compared with the sham-operated group, the myocardial fibrosis area of TAC mice was significantly increased, the mRNA and protein levels of TGF-β1 in the myocardium of the TAC group were increased, and the myocardial ROS level of TAC mice TUNEL staining showed that the apoptosis rate of cardiomyocytes in the TAC group was significantly increased, and the expression of SIRT1/AMPK pathway was decreased, but the effect of DAPA was the opposite, and the difference was statistically significant. Conclusion DAPA activates SIRT1/AMPK pathway signaling, thereby reducing cardiac fibrosis, hypertrophic remodeling, and myocardial oxidative stress.
2023, Vol. 20 
