The Protective Effect And Mechanism Of Ang(1-7) On Myocardial Injury After Cardiopulmonary Resuscitation In Rats

Objective: To investigate the effect of Ang(1-7)on myocardial damage after cardiac arrest-cardiopulmonary resuscitation(CPR)and the potential mechanisms.These will provide a new therapeutic basis for myocardial injury after resuscitation.Methods: To build the cardiac arrest-cardiopulmonary resuscitation model rat induced by ventricular fibrillation,seventy-two rats were randomly divided into sham group(n=18),control group(n=18),MasR agonist Ang(1-7)group(n =18)and MasR antagonist A779 group(n=18);dynamic monitoring of hemodynamics and cardiac function indexes of rats in each group,including HR,MAP,LVSP,and LVEDP,collected the myocardial and serum samples at 2h,4h and 6h after resuscitation;HE staining was used to detect the pathological damage of cardiomyopathy;cTnT and BNP expression levels in the serum were detected by colorimetry;ELISA method was used to detect the AngⅡ,Ang(1-7)in the serum and the expressions of SOD and MDA in myocardial tissue;the mRNA expression levels of AT1 R,AT2R,MasR,PI3 K and Akt in the myocardial tissue were detected by RT-PCR;Western Blot method was used to detect the protein expression levels of AT1 R,AT2R,MasR,PI3 K,pAkt and caspase-3 in myocardium.Results: 1.In cardiac arrest-cardiopulmonary resuscitation rat model,Ang(1-7)had an effect on myocardial function after resuscitation: Compared with sham group,the control group,Ang(1-7)group and A779 group of rats showed pathological damage,LVSP decreased,the LVEDP increased,the index of myocardial injury(cTnT)were increased,and the heart failure index(BNP)were increased,and the difference between the groups was statistically significant(P<0.05).Compared with the control group,Ang(1-7)group of rats LVSP index were lower,LVEDP index was higher,cTnT and BNP were reduced;the A779 group of rats had lower LVSP and higher LVEDP,cTnT and BNP were increased,the difference between the groups was statistically significant(P<0.05).2.Effects of exogenous Ang(1-7)on myocardial RAS after resuscitation: Compared with sham group,the rest of the three groups,the expression of AngⅡ were higher,the Ang(1-7)group of rats Ang(1-7)were higher in serum;the control and A779 group of rats AT1 R mRNA and protein expressions were higher,but the expressions of MasR mRNA and protein were lower;in Ang(1-7)group of rats MasR mRNA and protein expression were higher and AT1 R mRNA and protein expression were lower,the difference between the groups was statistically significant(P <0.05).Compared with the control group,Ang(1-7)group of rats Ang Ⅱwere lower and Ang(1-7)were higher in serum;A779 group of rats after resuscitation Ang wⅡ ere higher,Ang(1-7)were lower.In Ang(1-7)group,the expression of AT1 R mRNA and protein were lower and the expression of MasR mRNA and protein were higher.The A779 group of rats expressions of AT1 R mRNA and protein were increased and the expression of MasR mRNA and protein were decreased in myocardial tissue,the difference between the groups was statistically significant(P<0.05).3.Exogenous Ang(1-7)reduced the degree of myocardial injury and heart failure,and reduced apoptosis by regulating PI3K/Akt pathway: Compared with sham group,PI3 K,Akt mRNA and protein expression were higher in the other three groups;in the control group and Ang(1-7)group,SOD expression were higher and the expression of the A779 group were lower,while the MDA expression in the control group and the A779 group were higher and Ang(1-7)group were lower;the expression of caspase-3 in control group and A779 group were higher,the difference between the groups was statistically significant(P<0.05).Compared with the control group,the expression of PI3 K and Akt mRNA and protein in the myocardium of Ang(1-7)group were higher;the expression of PI3 K and Akt mRNA and protein were lower in the A779 group.The expression levels of SOD were higher in the myocardium of Ang(1-7)group,and the expression level of MDA were lower;in the A779 group,SOD were lower in the myocardium and the MDA expression were higher.In Ang(1-7)group,the expression level of caspase-3 were lower,and the expression of caspase-3 were higher in the A779 group,the difference between the groups was statistically significant(P<0.05).Conclusion:Ang(1-7)could improve the cardiac systolic and diastolic function in rat model after cardiopulmonary resuscitation(CPR),reduce cardiomyopathy pathological damage after recovery,and reduce the extent of myocardial tissue damage and heart failure after resuscitation.Ang(1-7)activated the PI3K/Akt signaling pathway by up-regulating MasR,with leading to alleviate myocardial oxidative stress and apoptosis,and reducing myocardial damage after cardiopulmonary resuscitation.