论文部分内容阅读
In patients with sepsis,lipopolysaccharide(LPS)from the outer membrane of gram-negative bacteria triggers cardiac dysfunction and heart failure,but target therapy for septic cardiomyopathy remains unavailable.In this study we evaluated the beneficial effects of cardamonin(CAR),a flavone existing in Alpinia plant,on endotoxemia-induced cardiac dysfunction and the underlying mechanisms with focus on oxidative stress and apoptosis.Adult mice were exposed to LPS(4 mg/kg,i.p.for 6 h)prior to functional or biochemical assessments.CAR(20 mg/kg,p.o.)was administered to mice immediately prior to LPS challenge.We found that LPS challenge compromised cardiac contractile function,evidenced by compromised fractional shortening,peak shortening,maximal velocity of shortening/relengthening,enlarged LV end systolic diameter and prolonged relengthening in echocardiography,and induced apoptosis,overt oxidative stress(O2-production and reduced antioxidant defense)associated with inflammation,phosphorylation of NF-κB and cytosolic translocation of transcriptional factor Nrf2.These deteriorative effects were greatly attenuated or mitigated by CAR administration.However,H&E and Masson's trichrome staining analysis revealed that neither LPS challenge nor CAR administration significantly affected cardiomyocyte cross-sectional area and interstitial fibrosis.Mouse cardiomyocytes were treated with LPS(4 μg/mL)for 6 h in the absence or presence of CAR(10 μM)in vitro.We found that addition of CAR suppressed LPS-induced defect in cardiomyocyte shortening,which was nullified by the Nrf2 inhibitor ML-385 or the NF-κB activator prostratin.Taken together,our results suggest that CAR administration protects against LPS-induced cardiac contractile abnormality,oxidative stress,apoptosis,and inflammation through Nrf2-and NF-κB-dependent mechanism.