Effects Of Different Exercise Preconditioning Strategies On Myocardial Mitochondrial Biogenesis,Fusion Fragmentation And Respiratory Function In Exhausted Rats

Objective:To investigate the differences in the protective effects of different intensity exercise preconditioning(EP)regimens on mitochondrial biogenesis,fusion division,and respiratory integrity in exhausted rats.To investigate the effects of EP on the peroxisome proliferator-activated receptor ? coactivator-1?(PGC-1?)and its downstream nuclear respiration factors 1 and 2(NRF1 and NRF2)and mitochondrial transcription factor A in exhausted rats.(TFAM)and the influence of the expression of mitochondrial dynamic-related protein 1(DRP1)and mitochondrial fusion protein 2(MFN2),and to observe their intervention effects on mitochondrial respiratory function.Method:1.60 healthy male SD rats were randomly divided into control group(C group),exhaust group(EE group),low-intensity exercise preconditioning + exhaustion group(LEP+EE group),moderate intensity exercise preconditioning + force.Exhaustive group(MEP + EE group),high-intensity exercise preconditioning + exhaustion group(HEP + EE group),12 in each group.Except group C,the rest of the groups referenced Bedford's treadmill exercise standards and established an animal model of exercise preconditioning through intermittent treadmill exercise.The speed is 30-36m/min,the exercise time is 96 min,and the slope is 3-6°.In the course of 96 minutes of exercise,every movement 12 min,rest 30 min,repeated 3 times.The slope of the running platform of the LEP+EE group is 3°,the speed is 30m/min,which is equivalent to 40%~50% VO2max;the gradient of the running platform of the MEP+EE group is 6°,the speed is 32m/min,which is equivalent to 65%~75% VO2max;HEP + EE group running slope is 6 °,speed is 36m/min,equivalent to 90% ~ 95% VO2 max.Exercise 5 days a week for a total of 8 weeks.Except for group C,one-time exhaustion exercise was performed after modeling was completed.Group C was drawn directly,and the rest of the groups were taken 30 minutes after exhaustion.Exhaustion Criterion: Rats remained in the back section of the runway more than 10 times in a row and photoacoustic stimulation was ineffective.2.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum creatine kinase(CK),creatine kinase isoenzyme(CK-MB)and troponin I(cTn-I)levels in each group.3.After the left ventricle myocardium specimens were processed,the respiration rate of the mitochondrial respiratory chain complexes I,II,and IV were determined by in situ method.4.The expression of PGC-1?,TFAM,NRF1,NRF2,MFN2,DRP1 protein in rat myocardial tissue was determined by Western Blot.Results:1.Comparison of serum biochemical parameters in rats.Compared with group C,except for CK-MB in MEP+EE group,the biochemical indicators in all other groups increased(P<0.05).Compared with the EE group,the biochemical indicators of the exercise preconditioning group were lower(P<0.05).Compared with LEP+EE group,serum biochemical indexes of MEP+EE group were lower(P<0.05).Compared with MEP+EE group,CK-MB index in HEP+EE group increased(P<0.05).2.Comparison of respiration rate of myocardial mitochondrial respiratory complex in each group.Compared with group C,the respiration rate of mitochondrial respiratory complexes in the other groups was decreased except the respiratory rate of RCR and complex II in compound I of MEP+EE group(P<0.05).Compared with the EE group,except for LEP+EE group II,IV and HEP+EE group II respiration rate,the rest of the groups were higher than the EE group(P<0.05).Compared with the LEP+EE group,the mitochondrial respiratory complex I,II,IV state 3 respiratory rate and complex I RCR values were all higher in the MEP+EE group(P<0.05).Compared with the MEP+EE group,the respiratory rate of composite I,IV state 3 and RCR of compound I were lower in the HEP+EE group(P<0.05).3.Comparison of PGC-1?,TFAM,NRF1,NRF2,and MFN2 expression in myocardium of rats in each group.Compared with group C,the expression of myocardial protein in the other groups was significantly decreased(P<0.05).Compared with EE group,the expression of myocardial protein in exercise preconditioning group was increased(P<0.05).The myocardial protein expression in the MEP+EE group was higher than that in the LEP+EE group and the HEP+EE group,and there was a significant difference between the LEP+EE group and the LEP+EE group(P<0.05).4.Comparison of DRP1 expression in myocardium of rats in each group.Compared with group C,the expression of DRP1 was higher in MEP+EE group(P>0.05),and the expression of DRP1 in other groups was significantly increased(P<0.05).The expression of DRP1 in EE group was higher than that in preconditioning group(P<0.05).Among them,the expression of DRP1 in myocardial tissue of MEP+EE group was lower than that of LEP+EE group and HEP+EE group(P<0.05).5.Correlation analysis of rat myocardial mitochondrial biogenesis related indicators.The PGC-1?,TFAM,NRF1,NRF2,MFN2,and DRP1 comparisons were strongly correlated and P<0.01.Conclusion:Exhaustive exercise reduces the number of myocardial mitochondria and decreases the mass of myocardium by downregulating the expression of PGC-1?-NRFs-TFAM pathway and MFN2,increasing the expression of DRP1,resulting in an imbalance of energy metabolism,resulting in myocardial damage,and inducing markers of myocardial injury.Abnormal increase.Exercise preconditioning stimulates mitochondrial biogenesis by upregulating the expression of PGC-1?-NRFs-TFAM signaling pathway and MFN2,while inhibiting the expression of DRP1,thereby increasing the number of new mitochondria and increasing the mitochondrial respiration rate.To reduce the effect of exhaustive exercise on myocardial mitochondrial energy metabolism,thereby reducing the exhaustive exercise on myocardial damage,play a role in myocardial protection.Different intensity exercise preconditioning programs have different effects on myocardial protection.The low-intensity exercise preconditioning scheme is the least protective;the high-intensity exercise preconditioning scheme is similar to the medium intensity scheme,but the high-intensity scheme has a higher risk and tendency of myocardial injury than the medium intensity;and the moderate-intensity exercise preconditioning scheme has an adverse effect on the heart.The risk is the minimum and the protection effect is the best.