| Objective: In this study,nuclear magnetic metabolomics analysis was used to establish the urine metabolic fingerprints of chronic unpredictable mild stress(CUMS)rats and to screen for metabolic markers to find the correlation between urine and exercise intervention in CUMS depression model rats.The differential metabolites and their metabolic pathways explore the mechanisms by which two different modes of exercise improve depressive symptoms.Methods: Chronic mild unpredictable stress + orphaned for 8 weeks to establish a CUMS rat depression model,and the blank control group(group C)was normally raised.The success or failure of the model was assessed by behavioral tests(body weight,sucrose preference rate,crossing and standing in open field test).After 4 weeks,the depressed rats were randomly divided into CUMS group(group D),aerobic exercise group(group A)and resistance exercise group(group R),8 rats in each group.After that,the rats in group D continued to model to maintain their depression,and the rats in group A and group R were given different exercise training at the same time,which continued for four weeks.Blood samples were taken from the abdominal aorta after the end of training to determine plasma serotonin(5-HT),brain-derived neurotrophic factor(BDNF)and corticosterone(CORT)levels.The ultrastructure of mitochondria in hippocampal CA1 region was observed by transmission electron microscopy.The NMR data were collected from the urine of each group by metabonomic technique and combined with multivariate statistical methods to analyze the changes of urine metabolites.Results: 1)After 4 weeks of modeling,the behavioral indexes of rats in group D,group A and group R were significantly lower than those in group C(p<0.01),indicating successful modeling.After 4 weeks of exercise intervention,compared with the group D,the sucrose preference rate,the number of crossing and standing in the group A and group R wereup-regulated(p<0.05,p<0.01).2)After 8 weeks,compared with the group D,the levels of 5-HT and BDNF in the plasma of group A and group R were significantly increased(p<0.05,p<0.01),and the level of CORT was significantly decreased(p<0.01).3)Compared with group C,rats in group D showed obvious mitochondrial swelling,blurred borders,partial membrane rupture,decreased matrix density,and loose mitochondrial lysis,resulting in“cavitation-like changes”.In contrast,the mitochondria morphology was generally normal in group A and group R,the number of mitochondria was large and the boundary was clear,the matrix was uniform,and the mitochondria were dense.4)Metabolomics results showed: compared with the group C,the levels of acetate,glycoprotein,glutamine,dimethylamine,methylguanidine,trimethylamine,creatine,putrescine,trimethylamine N-oxide,acetoacetate,malate,trigonelline,hippurate in urine of rats in group D increased,while the levels of acetone,pyruvate,α-ketoglutarate,citrate,malonate,glycine,creatinine and guanine decreased(P< 0.05,P < 0.01).Group A can significantly call back 5 potential biomarkers of glutamine,acetone,pyruvate,creatine and trigonelline(p<0.05,p<0.01).Group R can significantly call back 6 potential biomarkers of glutamine,acetone,α-ketoglutarate,citrate,creatine and trimethylamine N-oxide(p<0.05,p<0.01).5)Metabolic pathway analysis showed that aerobic exercise was mainly improved by regulating alanine,aspartate and glutamate metabolism,TCA cycle,glycolysis or gluconeogenesis,butyrate metabolism and pyruvate metabolism.Resistance exercise mainly through the regulation of alanine,aspartate and glutamate metabolism,TCA cycle to improve the urine metabolism characteristics of depressed rats.Conclusion:(1)Both aerobic and anti-respiratory exercises can effectively improve depressive symptoms in CUMS rats.(2)Several biomarkers in the urine that are commonly involved in the energy metabolism and amino acid metabolism showed beneficial changes in response to the exercise intervention.In particular,it was found thatresistance exercise had an obvious effect on TCA cycle.Furthermore,it was found that resistance exercise had an effect on intestinal microbial metabolism,while this effect was not found in aerobic exercise.(3)Both aerobic exercise and resistance exercise can improve the morphological structure of hippocampal mitochondria in CUMS rats.Exercise intervention can improve the urine metabolomics characteristics of depressed rats,especially the pathway related to energy metabolism,which may be related to the changes of hippocampal mitochondrial morphological structure. |
