RESUMO
Progressive macrophage dysfunction and apoptosis are some of the major events that occur during atherogenesis. To further investigate the intrinsic association between atherosclerosis (AS) and macrophage apoptosis and autophagy, cholesterol crystals (CHCs) were used to stimulate RAW264.7 macrophages to establish a macrophage model of advanced AS. Cells in the CHC group were treated with salvianolic acid B (Sal B) to evaluate its protective effects and reveal its underlying molecular mechanism. The results demonstrated that treatments with Sal B significantly improved autophagy dysfunction and reduced the apoptotic rate of CHCinduced macrophages. Furthermore, Sal B significantly attenuated CHCinduced release of proinflammatory factors (TNFα and IL6) by macrophages. Treatment of macrophages with a specific inhibitor of autophagy (3methyladenine) significantly reversed Sal Bmediated effects on autophagy, suggesting that Sal Binduced autophagy may display a protective effect in CHCinduced macrophages. Furthermore, pretreatment of CHCinduced macrophages with insulin significantly decreased Sal Binduced autophagy, indicating that the Akt/mTOR signaling pathway may serve as a critical mediator in regulating Sal Bmediated cell death. Taken together, the present study demonstrated that Sal B improved autophagic dysfunction and reduced the apoptosis of CHCinduced macrophages via inhibiting the Akt/mTOR signaling pathway.