Aerobic Exercise Down-regulates Myocardial Infarction Heart ALCAT1 And Inhibits Myocardial Mitochondrial Autophagy And Damage

Objectives:To investigate the effect of aerobic exercise on endogenous ALCAT1 in rats with myocardial infarction(MI)and the relationship with inhibiting myocardial mitochondrial autophagy with injury,and to provide the basis for the treatment of myocardial infarction.Methods:60 male SD rats aged 3 months were Randomly divided into normal group(C),normal aerobic exercise group(CE),sham operation control group(Sham,S),12 rats per group The remaining rats were ligated with the left coronary artery permanently,with 24 survival after operation,randomly divided into myocardial infarction(MI)and myocardial infarction+ aerobic exercise group(ME).The S group only opened the chest without ligation.The ME group underwent four weeks of aerobic exercise after a week of surgery.The rats were executed after training,the hearts were quickly removed from thorax,flushed by precooling 0.9%saline,stripping pericardium,bloted with filter paper,and weighed.Fringe area samples cutted from the heart of broken neck rats were quickly into the precooling of electron microscope fixed fluid,4?stored.Mitochondria morphology and autophagy was observed by transmission electron microscope,expression of ALCAT1mRNA,mitochondria DNA,mitochondrial membrane potential was detection.The expression of LC3 II,P62,ALCATI,Parkin,PINK1,ANP,BNP,MFN2,VDAC1,COX I,SOD were detected by Western Blot method,the activity of enzyme of myocardial antioxidant system(CAT,GPX,T-AOC)was detected with ELISA kit.Results:(1)The results of transmission electron microscopy showed that the myocardial fibers of control rats were orderly arranged,the leap disc was clear,and the mitochondrial cristae formed by endometrium depression was dense and orderly.The mitochondria in rats density increases,the volume increase after exercise.mitochondria swelling,compensatory hyperplasia,myofibril dissolution,part of the intercalated disc expansion,increased autophagosome in rats with myocardial infarction,mitochondria swelling was alleviate and sarcomere intercalated disc structure was clear with myocardial infarction after exercise.(2)The expression of ALCAT1 protein in myocardial infarction was significantly increased,and it can be significantly reduced by aerobic exercise.(3)The expression of LC3?/LC3? protein were significantly increased in rats with myocardial infarctionand P62 protein were significantly decrease(p<0.01),aerobic exercise could down-regulated the expression of LC3-? protein(p<0.01).Indicate that myocardial autophagy was increased in rats with myocardial infarction significantly and P62was increased,exercise can reduce myocardial autophagy.(4)mtDNA and mitochondrial membrane potential(JC-1)were significantly reduced in rats with myocardial infarction(p<0.05),and mtDNA and mitochondrial membrane potential(JC-1)were significantly increased after aerobic exercise.Indicate thatthe myocardial mitochondrial function is blocked after myocardial infarction,and aerobic exercise can significantly improve myocardial mitochondrial function in rats with myocardial infarction.(5)Myocardial infarction resulted in a significant decrease of COX PINK1 Parkin and MFN2 protein(p<0.01,p<0.05),aerobic exercise can significantly increase the expression of COX PINK1 Parkin and MFN2 in myocardial myocardium(p<0.01,p<0.05).Indicate thaterobic exercise significantly reduced the pathway of mitochondrial autophagy.mediated by PINK1.(6)The level of anti-oxidative stress parameters(T-AOC,CAT,GPX,SOD)were significantly reduced in rats with myocardial infarction,and all of them increased significantly after aerobic exercise.Indicate thatanti-oxidative capacity of myocardium caused by myocardial infarction significantly decreased,and aerobic exercise significantly increased the anti-oxidant capacity of myocardium.(7)The expression of ANP and BNP protein was significantly increased in rats with myocardial infarction(p<0.01),and aerobic exercise significantly decreased the expression of myocardial ANP and BNP protein in myocardial infarction(p<0.01).Indicate that myocardial disfunction occured after myocardial infarction,aerobic exercise can significantly reduce the degree of myocardial injury.Conclusions:1.The mitochondria of rats with myocardial infarction showed compensatory hyperplasia,swelling and dissolving of myofibril,and disappearing of the disc,up-expression of ANP and BNP protein.This condition can be improved after 4 weeks of aerobic exercise.Indicate thataerobic exercise can reduce the damage of myocardial mitochondrial structure and myocardial disfunction.2.Due to the fact that the myocardial ALCAT1 and oxidative stress are a cause and effect.The protein and gene expression of ALCAT1 significantly increased,and the anti-oxidant capacity of myocardium,expression of COX ??PINK1?Parkin and MFN2 proteins significantly dcreased.Aerobic exercise significantly reduced the protein and gene expression of ALCAT1,significantly increased the anti-oxidant capacity of myocardium,expression of COX ??PINK1?Parkin and MFN2 proteins.It is speculated that aerobic exercise can alleviate myocardial mitochondria structure damage and function damage,which is realized by inhibiting myocardial ROS and ALCAT1 level,thereby inhibiting mitochondrial autophagy PINK1/Parkin mediated.