Observation of the therapeutic effect of dapagliflozin on atherosclerosis in mice and preliminary exploration of the mechanism of action.

In recent years, the incidence of Atherosclerosis (AS) has been increasing and has gradually become a major disease threatening human health. In this study, we analyzed the effect of dapagliflozin on AS and preliminarily explore the mechanism of action. First, apolipoprotein E (ApoE) knockout C57Bl/6J mice were used to establish an AS model in vitro. An intervention group treated with dapagliflozin and a model group treated with normal saline, both administered by gavage, were set up. The effects of dapagliflozin on macrophage polarization, blood lipids, inflammation, oxidative stress, and vascular adhesion of AS mice were observed, we found that compared with the model group, macrophages in the intervention group of mice were polarized from M2 to M1 type, the levels of inflammatory factors in the intervention group decreased, and the oxidative stress reaction and vascular adhesion were inhibited. Subsequently, the aorta tissues of mice were stained with HE and oil red O to observe their histopathological changes. We observed a significant improvement in aortic pathologic damage in the intervention group, converging to normal mice. Finally, autophagy in mouse aortic cells was determined, found the intervention group showed markedly increase Beclin-1 and LC3-II expression in the aorta than the model group. In conclusions, dapagliflozin can ameliorate the progression of AS, and its mechanism is related to the activation of aortic cell autophagy.