The Effects Of HIIT On Myocardial AMPK/Sirt1/NF-?B Signaling Pathway Mediated Inflammation In SAMP8 Mice

Research background and purpose: In recent years,with the rapid growth of population ageing,people pay more attention to the aging phenomenon,especially the decline of cardiovascular function,the decline of skeletal muscle strength,and the increase in the proportion of agerelated diseases.In order to delay myocardial aging and reduce the occurrence of senile heart disease,we should strengthen the research on the mechanism of myocardial aging.Based on the theory of Aging Inflammatory Cytokines,this study was designed to investigate the effect of high intensity interval training(HIIT)on aging in SAMP8 mice,then the effects of HIIT on myocardial inflammation and related cytokines in Samp8 mice were observed to explore the effect of HIIT on delaying myocardial aging.To observe the experimental results,to study whether HIIT has anti-inflammatory effect on Aging Myocardium,so as to provide a further theoretical basis for reducing the level of inflammatory response of aging myocardium.Research methods: In this experiment,20 male SAMR1 mice aged 4 months and 20 male Samr8 mice aged 4 months were selected,and their body weight was about 22-28 g.Samr1 mice were randomly divided into two groups: Normal Contral Group(NC)and Normal HIIT group(NH),and Samr8 mice were randomly divided into two groups: Model Contral Group(MC)and Model HIIT group(MH),10 in each group.Three days a week,every other day for 16 weeks.The training time is from 17:00 to 19:00,and the rest is 4 days a week.In the first week,all the mice were given 3 times of adaptive training,the training program was: 20 minutes of 5M / Min treadmill training.At the 2nd-16 th week,the training load was set as 20m/min(1min)+8m/min(2min)as a group,and the training cycle was 16 groups.After training,the 8 groups rested for 10 minutes,and the training lasted for about 1h.All your workouts should be at a zero degree incline.After adaptive training,Nh and MH groups were given highintensity intermittent exercise.After 16 weeks,all the mice were anesthetized 24 hours after the last training.The relative mRNA expression levels of AMPK ?2,Sirt1,NF-?B p65 and TNF-? were detected by RTPCR,and the relative protein expression levels of p-AMPK 2,Sirt1,NF-?B p65 and TNF-? were detected by Western Blotting.The results were analyzed with GRAPHPAD Prisim 8,and the experimental data were analyzed with one-way Anova.Research results:(1)At the end of the exercise intervention,the body weight of all groups of mice increased after the experiment,with an average increase of 4.66 g per group.After comparing the body weight before and after the experiment,the Body Weight of NC group mice increased significantly(P<0.01).(2)The results of HE staining showed that in NC group,the CYTOPLASM was pink,the nucleus was blue-purple,and the myocardial fibers were closely arranged.In NH Group,the arrangement of myocardial fibers was regular,the morphology of myocardial cells,cytoplasm,intercellular substance and transverse(longitudinal)Stria were normal.Compared with NC Group,MC Group showed disordered arrangement of cell fibers,increased intercellular space and increased inflammatory infiltration.Compared with NH Group,MH group had more cell rupture,disordered fiber arrangement,larger intercellular space and more inflammatory infiltration.(3)Compared with mice in the NC group,TNF-? mRNA expression decreased significantly in the NH group(P<0.01);The expression of TNF-? protein in mice in the MC group increased significantly(P<0.01).Compared to mice in the MC group,the expression of TNF-? protein in the MH group decreased significantly(P<0.05).Compared to mice in the NH group,TNF-? protein expression in the MH group increased significantly(P<0.05).(4)Compared to mice in the NC group,the expression of AMPK ?2 protein in The NH group increased significantly,the AMPK ?2 mRNA expression and the p-AMPK ?2 protein expression in the MC group both decreased significantly(P<0.01);Both mRNA expression and p-AMPK ?2 protein expression decreased significantly(P<0.01),while both AMPK ?2 mRNA expression and p-AMPK ?2 protein expression decreased significantly(P<0.05)compared to mice in the NH group.(5)Compared to mice in the NC group,Sirt1 mRNA expression decreased significantly in mice in the NH group(P<0.01),and Sirt1 protein expression increased significantly in MC group mice(P<0.05);mRNA expression decreased significantly(P < 0.01),Sirt1 protein expression decreased significantly in mice in the MH group(P<0.05);(6)Compared to mice in the NC group,the expression of NF-?B p65 mRNA in the NH group decreased significantly(P<0.01),the expression of NF-?B p65 protein in MC group mice increased significantly(P<0.05)?Research conclusions:(1)SAMR1 mice and SAMR8 mice have different levels of myocardial inflammatory response,which is mainly due to the increase of myocardial inflammatory response with the rapid aging of SAMR8 mice.(2)HIIT could effectively reduce the expression of TNF-? mRNA and protein in Myocardium of SAMP8 mice,indicating that TNF-? could inhibit the proinflammatory effect in the process of HIIT intervention.(3)HIIT can activate AMPK/Sirt1/NF-?B signal pathway in SAMP8 mice,which may be by promoting the expression of AMPK and Sirt1 in myocardium and inhibiting the activation of NF-?B,thus controlling the expression of downstream inflammatory genes and delaying the inflammatory aging of myocardium.