BACKGROUND AND PURPOSE: Sepsis is a @entity1850 accompanied by excessive production of inflammatory cytokines and @entity65 . Importantly, macrophage-derived pro-inflammatory response plays a key role in septic @entity65 . This study aimed to investigate the effects of @entity1481 ( @entity2904 ) on macrophage pro-inflammatory response in endotoxin-induced @entity296 . EXPERIMENTAL APPROACH: @entity19 pretreated with @entity2904 were challenged with lipopolysaccharide (LPS) by intraperitoneal injection and cardiac function was evaluated. Levels of macrophage infiltration, macrophage inflammatory response and cardiomyocyte apoptosis were examined using immunohistochemical staining, ELISA, RT-PCR, Western blot, TUNEL and flow cytometry assay. KEY RESULTS: Results showed that @entity2904 pretreatment prevented LPS-induced @entity296 and apoptosis. Consistently, @entity2904 lowered levels of proinflammatory cytokines in serum and heart tissue and myocardial macrophage infiltration. Bone marrow transplantation indicated that @entity2904 alleviated LPS-induced @entity296 via decreasing macrophage infiltration. @entity2904 reduced proinflammatory cytokines expression in LPS-stimulated cardiac and peritoneal macrophages. Co-culture of @entity2904 pretreated macrophages with cardiomyocytes and conditioned media from @entity2904 pretreated macrophages both decreased LPS-induced cardiomyocyte apoptosis. The anti-apoptosis effects of @entity2904 resulted from the reduction of proinflammatory cytokines, which achieved partially by normalizing the @entity14075 /AMPK/ @entity10182 / @entity10183 and @entity14075 / @entity3229 pathway in macrophages. Meanwhile, secretions of cytokines were also regulated by ROS, which were attenuated by @entity2904 via activation of @entity14075 , AMPK and @entity3229 . CONCLUSIONS AND IMPLICATION: In conclusion, @entity2904 protected against LPS-induced @entity296 and apoptosis, associated with inhibition of macrophage pro-inflammatory response. Our studies suggest that @entity2904 might represent a novel therapeutic agent to prevent and treat @entity295 induced @entity296 .

@entity1481 prevents macrophage mediated septic @entity296 via XXXX .

@entity296 :: ('MESH:D009202', 'Disease') :: ['myocardial dysfunction'] @entity3229 :: ('19013(Tax:10090)', 'Gene') :: ['PPARa'] @entity10182 :: ('18024(Tax:10090)', 'Gene') :: ['Nrf2'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity19 :: ('10090', 'Species') :: ['Mice'] @entity14075 :: ('93759(Tax:10090)', 'Gene') :: ['Sirt1'] @entity1850 :: ('MESH:D018746', 'Disease') :: ['systemic inflammatory response syndrome'] @entity1481 :: ('MESH:D014292', 'Chemical') :: ['trimetazidine'] @entity2904 :: ('CHEBI:72564', 'Chemical') :: ['TMZ'] @entity10183 :: ('15368(Tax:10090)', 'Gene') :: ['HO-1'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular dysfunction', 'cardiovascular impairment']
@entity14075 :: (93759(Tax:10090),Gene) :: ['Sirt1']
