The Role Of Radix Pseudostellariae Polysaccharides In The Anoxia/reoxygenation-induced Cardiomyocyte Necroptosis

BackgroundThe morbidity and mortality of acute myocardial infarction(AMI)are increasing nowadays.The AMI is one of the main causes of human death.Ischemic and hypoxic condition leads to irreversible damage to cardiomyocyte in AMI.Timely reperfusion therapy which includes thrombolysis therapy and percutaneous coronary intervention treatment is effective means of the treatment of acute myocardial infarction.However,the reperfusion induces additional injury to the myocardium termed ischemia/reperfusion(I/R)injury.I/R injury can lead to apoptosis,necrosis and inflammatory response in myocardial cells.Necroptosis is a programmed necrosis.Necroptosis is controlled by receptor interacting protein kinase-3(RIPK-3).Necroptosis plays an important role in myocardial ischemia/reperfusion injury.Radix pseudostellariae(RP)is a root of the Pseudostellaria heterophylla(Miq.)Pax,which contains cyclic peptide,triterpenoid saponins,polysaccharides and other components.RP can improve chronic heart failure,memory loss and has other pharmacological effects.Radix pseudostellariae polysaccharides(RPPs)plays a significant role in anti-oxidative stress,anti-inflammatory,and immune regulation.ObjectiveThe aim of the study is to evaluate the role and mechanism of RPPs in cardiomyocyte necroptosis induced by anoxia/reoxygenation.MethodsThe anoxia/reoxygenation(A/R)challenge to cultured cardiomyocytes to mimic myocardial I/R in vivo.The cardiomyocytes of SD rats were divided into 3 groups:control group,A/R group,and A/R with RPPs group.The cardiomyocyte RIPK3levels?LDH release?PI staining and survival rate of cardiomyocytes were used as indices for determination of cardiomyocyte necroptosis..Results1.RPPs has no toxic effect on na?ve cardiomyocytes2.RPPs significantly attenuates cardiomyocyte necrosis as indicated by decreasing in cardiomyocyte LDH release,increasing in survival rate of cardiomyocytes,reducing PI staining of the cardiomyocytes after A/R.3.RPPs significantly reduces the expression of RIPK3 in cardiomyocyte after A/R.ConclusionOurs results suggest that the RPPs protects cardiomyocytes from A/R-induced necroptosis via down regulation of RIPK3.