Exercise Preconditioning Induces Cellular Autophagy By Intermittent Ischemia-Hypoxia To Participate In Early Myocardial Protection

Objective: Intermittent high-intensity exercise results in repetitive and transient ischemia,allows the myocardium to be protected during subsequent myocardial injury induced by acute stress,which can protect the myocardium from prolonged ischemia and hypoxia,the type of such exercise,is called exercise preconditioning(EP).Cellular autophagy selectively degrades and reuses intracellular senescent and damaged organelles or proteins in lysosomes.The occurrence of autophagy is regulated by a variety of signaling pathways.Beclin1,as a convergent point for multiple signaling pathways,plays a crucial regulatory role through interacting with Bcl-2.By analyzing the relationships between myocardial ischemia-hypoxia and cellular autophagy in exercise,and by detecting changes of autophagy-associated proteins Beclin1/Bcl-2 in early exercise preconditioning(EEP)and in early protective phase,the effects of cellular autophagy on EEP-cardioprotection were discussed.Methods: SD rats were randomly divided into the groups of control(C group),early exercise preconditioning(EEP group),exhaustive exercise(EE group),and early exercise preconditioning + exhaustive exercise(EEP+EE group).After establishing of EP animal model,exhaustive exercise on treadmill for inducing myocardial injury.1)Plasma cTnI contents were detected by chemiluminescence immunoassay(CLIA)method,which were combined with the adjacent slices between HE-staining and HBFP-staining,to comprehensively assess the extents of myocardial ischemia-hypoxia,and to verify the EEP-cardioprotection.2)The expressional changes and the dissociated degrees in Beclin1/Bcl-2 were detected by immune-blotting,and were observed by double-labeling immunofluorescence,respectively.3)The relationships between exercise-induced hypoxia-ischemia and cellular autophagy were assessed by the correlational analysis.Results: 1)Compared with the C group,the plasma cTnI levels and the MOD values in the EEP group to both have increasing tendencies(P>0.05),and these in the EE group and in the EEP+EE group to were both significant increase(P<0.05).Compared with the EE group,the plasma cTnI levels and the MOD values in the EEP group to were both significant decrease(P<0.05).Compared with the C group,all other groups to represent ischemia-hypoxia changes in different degree,which were as the acidophilyenhanced positions in HE-staining approaching to the positive areas of crimson in HBFP-staining.2)Compared with the C group,all other groups to have significantly increased Beclin1 levels(P<0.05),and to have increased extents of Beclin1/Bcl-2 dissociations(P<0.05),but which were without any changes in Bcl-2 levels.Compared with the EE group,the extents of Beclin1/Bcl-2 co-localization were significant increase(P<0.05).All groups represented with significantly negative correlations between the Beclin1/Bcl-2 co-localization and the ischemia-hypoxia areas,and the IOD values respectively.Conclusion: EP can upregulate the expression of autophagy-related protein Beclin1 and promote the dissociation of Beclin1/Bcl-2 complex through intermittent myocardial ischemia and hypoxia,which can induce autophagy in cardiomyocytes.Autophagy participates in the early protection of EP against exhausted exercise-induced myocardial injury.