The Correlation Study Of Effect Of Exercise Training On Apelin/APJ System And Mechanism Of Improve Cardiac Aging In Mice

ObjectiveOur research aimed to state that exercise training can improve the cardiac aging phenotype of mice,To investigate the effect of exercise training on Apelin / APJ system and its relationship with cardiac aging,To explore the potential mechanism of exercise training affecting cardiac aging through Apelin / APJ system.MethodWe used the 24-week-old SPF grade SAMP8 mice as an aging mouse model.APJ antagonist F13 A was applied as an inhibitor of Apelin.48 male SAMP8 mice weighing25-30 g were randomly divided into 4 groups: 1.Sedentary-control Group;2.Sedentary-F13 A group;3.Exercise training-control group;4.Exercise training-F13 A group.The sedentary group did not receive exercise treatment.The exercise group received 6 weeks of moderate-intensity treadmill exercise training with a speed of 15meters/minute,a duration of 60 minutes/session,and a frequency of 5 days/week.The F13 A group was intraperitoneally injected with 75 μg/kg of F13 A solution every day,and the control group was intraperitoneally injected with 75 μg/kg of normal saline every day.At the end of exercise training,the serum of the mice in each group was gained.After the mice sacrificed,the myocardium was collected.The serum Apelin of the mice in each group was detected by ELISA.the expression of APJ in the myocardial tissue were detected by immunohistochemistry.HE and MASSON staining was used to detect cardiac aging.WB and PCR were applied to detect energy metabolism,mitochondrial autophagy and mitochondrial dynamic related markers.Result1.After 6 weeks of intervention,the serum Apelin concentration of the ET-C group and Sed-F group were significantly higher than that of the Sed-C group.The expression of APJ of the myocardial tissue was higher in the ET-C group than that of Sed-C group.2.After 6 weeks of intervention,the degree of changes in myocardial tissue morphology and fibrosis was obvious in the Sed-F group a certain extent in Sed-C and ET-F groups,and little in the ET-C group.Compared to the Sed-C group,ET-C group had a lower level in the protein and mRNA expressions of the aging markers-P16 and P21.However,the P16 and P21 expression was increased in ET-F group than that of ET-C group.3.After 6 weeks of intervention,there was no significant difference in the protein and mRNA expression of glucose metabolism marker-GLUT1 across 4 groups.Compared to Sed-C group,the protein and mRNA expression of the lipid metabolism marker-CPT-1A in the myocardium of the ET-C group increased significantly.The expression of CPT-1A was lower in the ET-F group,compared with the ET-C group.Compared with the Sed-C group,the mRNA expression of mitochondrial autophagy markers PINK1 and PARKIN in the myocardial tissue of the ET-C group was significantly reduced.There was no significant difference in the mRNA expression of PINK1 or PARKIN between ET-C and ET-F group.Compared with the Sed-C group,the ET-C had a lower expression of mitochondrial fission markers FIS1 and MFN in the myocardial tissue.While the mRNA expression of the fusion-related molecules OPA1 and DRP1 was significantly increased in ET-C group.There was no significant difference in the mRNA expression of mitochondrial dynamics markers FIS1,MFN,OPA1,and DRP1 between ET-C and ET-F group.Compared with that of the Sed-C group,the protein and mRNA expression of the mitochondrial biogenesis marker PGC-1α in the myocardium of the ET-C group was significantly increased.Compared to the ET-C group,the ET-F group had lower expression of PGC-1α.There was no significant difference in the mRNA expression of the mitochondrial biogenesis markers PPAR-αand NRF between ET-C and ET-F group.Conclusion1.Moderate intensity exercise training can increase the serum Apelin concentration in aging mice.2.Moderate intensity exercise training can improve the cardiac senescence phenotype of mice.Meanwhile it increased myocardial lipid metabolism,mitochondrial biogenesis and mitochondrial fussion.In addition,it reduced mitochondrial autophagy and mitochondrial fission.3.Moderate intensity exercise training may improve cardiac senescence phenotype through improving myocardial lipid metabolism and biogenesis by activating Apelin/APJ system.