Cardamonin protects against lipopolysaccharide-induced myocardial contractile dysfunction in mice through Nrf2-regulated mechanism  

作　　者：Ying Tan Hong-hong Wan Ming-ming Sun Wen-jing Zhang Maolong Dong Wei Ge Jun Ren Hu Peng 

机构地区：[1]Department of Emergency Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [2]Department of Burns,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [3]Center for Cardiovascular Research and Alternative Medicine,University of Wyoming College of Health Sciences,Laramie,WY 82071,USA [4]Department of Emergency,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,China [5]Department of General Practice,Xijing Hospital,the Air Force Military Medical University,Xi'an 710032,China

出　　处：《Acta Pharmacologica Sinica》2021年第3期404-413,共10页中国药理学报（英文版）

基　　金：supported in part by the National Natural Science Foundation of China(81671938,81571895).

摘　　要：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(O_(2)^(−)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(4µg/mL)for 6 h in the absence or presence of CAR(10μM)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.

关 键 词：CARDAMONIN LIPOPOLYSACCHARIDE cardiac dysfunction INFLAMMATION apoptosis oxidative stress 

分 类 号：R96[医药卫生—药理学]