Plasma Metabolomics Mechanism Of Different Modes Of Exercise In Improving Depressive Symptoms In CUMS Rats

Objective: To explore the different metabolites and metabolic pathways in plasma of CUMS depression model rats under different exercise modes based on metabonomics analysis technology,and to analyze the mechanism of different exercise modes to improve depressive symptoms in combination with the changes of plasma antioxidant index.Methods: 72 male SD rats were randomly divided into 6 groups,including control group(C),depression group(D),pre-exercise group(P),aerobic exercise group(A),resistance exercise group(R)and aerobic + resistance exercise group(AR).All rats in the experimental group were induced by CUMS stress at the first four weeks.At the fourth week,the rats with depressive symptoms were randomly divided into D group,P group,A group,R group and AR group according to their behavioral indicators.In the P group,aerobic exercise intervention was conducted for 4 weeks at the same time,and rest groups were rested.In the later 4 weeks,group D continue to be given CUMS stress,aerobic intervention was conducted in group P and group A,resistance intervention was conducted in group R,and aerobic+resistance intervention was conducted in group AR.In order to prevent the self-healing of rats,exercise groups were given mild stress at the same time of exercise intervention.Group C was fed for 8 weeks.During the experiment,the weight and behavioral indexes of rats were followed up every week.After 8 weeks,the antioxidant indexes(SOD and MDA)and 1H-NMR metabolomics were measured in plasma.Result:(1)After 4 weeks of modeling,there were significant differences in behavioral indicators(sugar preference,number of erections)between group C and group D(p < 0.05,P < 0.01).There were significant differences in behavioral indicators between group P and group D(p < 0.05),there was no significant difference between group P and group C.The body weight of rats in group D,P,A,R and AR were significantly different from those in group C(p < 0.01).(2)After 4 weeks of exercise,there were significant differences in behavioral indexes between group C and group D(p < 0.05).There were no significant differences in behavioral indexes between group P,group A,group R and group AR,except body weight index(p < 0.01).(3)After 8 weeks,compared with group C,SOD activity in group D decreased significantly(p < 0.01)and MDA content increased significantly(p < 0.01).After 4 weeks of exercise,compared with group D,SOD data in group P,group A,group R and group AR increased significantly(p < 0.01),while MDA content decreased significantly(p < 0.05,P < 0.01).(4)After 4 weeks,compared with group C,15 biomarkers were identified in group D(p < 0.05,P < 0.01,P < 0.001).After exercise intervention,group P could regulate 6 biomarkers(p < 0.05,P < 0.01,P < 0.001),including ketone synthesis and degradation,butyric acid metabolism and inositol phosphoric acid metabolism.Metabolic pathway;Group A can regulate six metabolites of N-acetyl glycoprotein,leucine,lactic acid,low density lipoprotein,glucose and acetoacetate(p < 0.05,P < 0.001),involving three metabolic pathways of ketone synthesis and degradation,butyric acid metabolism and branched chain amino acid biosynthesis;Group R can regulate six metabolic pathways of choline,lactic acid,inositol,glucose,phosphocreatine and acetoacetate.Compounds(p < 0.01,P < 0.001)involve three metabolic pathways: ketone synthesis and degradation,butyric acid metabolism and inositol phosphoric acid metabolism;AR group can regulate five metabolites of choline,citric acid,glucose,acetone and acetoacetic acid(p < 0.05,P < 0.01,P < 0.001),involving ketone synthesis and degradation,butyric acid metabolism,glyoxylic acid and dicarboxylic acid metabolism.Conclusion:(1)Pre-exercise for 4 weeks can effectively delay the establishment of depression model in CUMS rats.(2)The effects of different exercise modes on plasma antioxidant indexes in the rat model of CMUS depression are related to the changes of plasma metabolites.(3)Depressive symptoms in CUMS depressive rats can be improved by different exercise,which are related to different metabolic pathways involved.Pre-exercise and resistance exercise have common metabolic pathways in metabolome.