| The national economy is greatly improved Nowadays,the social environment is also more complicated.People often face tangible and intangible pressures from all sides,leading to an increase in the incidence of depression..The study reports that depression is expected to become the world fatality rate in 2020.The disease with the second highest disability rate and the high recurrence rate of depression are the hotspots of research at home and abroad.In depression,abnormal kynurenine metabolism is one of the mechanisms that can not be ignored.KYN in kynurenine metabolism in the central nervous system can accumulate depression,and KYN60% in the brain comes from the periphery,while the periphery KYN can be converted into KYNA under the enzymatic reaction of KATs,thereby reducing the KYN content that can penetrate the blood-brain barrier,avoiding the accumulation of neurotoxic KYN in the central nervous system,and improving the effect of depression.Aerobic exercise is effective in improving depression,but its mechanism remains to be elucidated.Previously,most of the research at home and abroad focused on the central nervous system.In recent years,the field of sports medicine has begun to report that exercise plays an antidepressant role by regulating skeletal muscle-related factors,and PGC-1α has to be mentioned.PGC-1α is a susceptibility factor for exercise training inskeletal muscle.Aerobic exercise can up-regulate the expression of PGC-1α in skeletal muscle.PGC-1α can promote the expression of KATs,and transform the peripheral KYN metabolism into KYNA pathway.Regulation of the uridine metabolism pathway.miRNA is a hotspot in physiological and biochemical research in recent years.Multiple miRNAs have been found in animal models and clinical depression patients,including miRNA-130 b.miRNA-130 b has been monitored in patients with depression,suggesting that miRNA-130 b may play a role in the development of depression.PCG-1α has been shown to be a direct target of miRNA-130 b.However,in depression,can aerobic exercise improve the depression through the miRNA-130 b / PGC-1α/KATs pathway? This issue is still unclear.Objective: This study explores the effects of aerobic exercise on miRNA-130b/PGC-1α / KATs pathway-related factors in depression by establishing a mouse model of chronic unpredictable stress depression and aerobic exercise intervention model.The mechanism of exercise regulation of miRNA-130b/PGC-1α/KATs pathway in skeletal muscle in mice with depression attempts to provide a meager theoretical basis for aerobic exercise to improve the possible pathways of depression.s for the possible ways of aerobic exercise to improve depression.Methods: 45 healthy male KM mice were randomly divided into 3groups.They were the control group(CG group,N=15),the modelcontrol group(MG group,N=15),and the model aerobic exercise group(ME group,N=15).The control group received routine feeding and no exercise;the model group and the aerobic exercise model group used 12 stress factors to stimulate the mouse depression model for 28 days.On the third day after the successful model construction,the model group began routine feeding,and no Exercise;the model aerobic exercise group began the 6th week after the aerobic exercise intervention,the exercise program was 10 m / min,60 min / d,6d / w;respectively in the first group day,the end of modeling,Behavioral tests were conducted after the end of the exercise intervention.The test contents were: tail suspension experiment,sugar water consumption experiment,open field experiment,forced swimming experiment.After 24 hours of the last behavioral test,the three groups of mice were anesthetized separately to take quadriceps and brain tissue;Elisa kit was used to test the KYN content in mouse skeletal muscle and brain tissue;Westren blot was used to determine mouse skeletal muscle PGC-1α,KAT1,KAT3,KAT4 protein expression;RT-PCR method to detect mRNA expression of skeletal muscle miRNA-130 b,PGC-1α,KAT1,KAT3,KAT4.Results:(1)Body mass and behavioral test results:(1)28 days of chronic unpredictable stimulation can cause significant mental decline in mice,such as decreased body mass,decreased appetite,dull gaze,and dislike movement.After the end of the exercise intervention experiment,the MG group still did not improve significantly,but the ME group improved significantly after the end of exercise intervention.(2)After the end of modeling,the body mass test results: chronic stress stimulation led to small MG group and ME The weight gain of the rats was lower than that of the CG group,but there was no significant difference(P>0.05).After the aerobic exercise intervention,the body weight of the MG group and the ME group was lower than that of the CG group,and the MG group was lower than the ME group,and there was no significant difference(P>0.05).(3)Behavioral scores: After 28 days of chronic stimulation intervention,the scores of the tail suspension experiment,forced swimming experiment,open box experiment and sugar water consumption experiment were significantly different between the MG group and the ME group compared with the CG group(P<0.01);After the end of the oxygen exercise intervention,the scores of the ME group compared with the MG group were significantly different(P<0.01).The scores of the ME group compared with the CG group decreased,but there was no significant difference(P>0.05).(2)Western blot results:(1)PGC-1α: PGC-1α expression in skeletal muscle was significantly higher in CG >ME >MG,ME group and CG group were significantly different from MG group(P<0.01).The ME group was lower than the CG group but there was no significant difference.(2)KATs: Compared with CG group,the expressions of KAT1,KAT3 and KAT4 in MG group were significantly down-regulated(P<0.01).In addition,compared with MG group,KAT1 and KAT4 in ME group were significantly up-regulated(P<0.05).KAT3 was elevated,but there was no significant difference(P>0.05).(3)RT-PCR results:(1)miRNA-130b: Compared with CG group,it was significantly down-regulated in MG group(P<0.05);ME group was down-regulated compared with MG group,and the down-regulation trend was also significant(P<0.05).(2)PGC-1α: Compared with CG group,the expression of PGC-1α mRNA in skeletal muscle was significantly down-regulated in MG group(P<0.01).The expression of PGC-1αmRNA in ME group was significantly higher than that in MG group.There was a very significant difference(P<0.01)and lower than the CG group(P<0.05).(3)KATs: Compared with the GC group,the mRNA of KATs was down-regulated in the MG group,and the expression of KAT1 was slightly down-regulated,which was not statistically significant(P>0.05).KAT3 was down-regulated by 21%,and there was a significant difference compared with the CG group(P<0.05).The KAT4down-regulation trend was the most significant(P<0.01).Exercise intervention showed a significant up-regulation of KATs expression.Compared with CG group,KAT3 and KAT4 were significantly up-regulated(P<0.01)and KAT1 was up-regulated(P>0.05).KAT3 and KAT4 were significantly up-regulated in ME group compared with MGgroup(P<0.01),and KAT1 was also significantly up-regulated(P<0.05).(4)Elisa results:(1)skeletal muscle: Compared with CG group,KYN content in MG group and ME group were significantly different(p<0.01),and the content of MG group increased significantly.The content of ME group was lower than that of MG group,but there was no significant difference(p>0.05).(2)Brain tissue: Compared with the CG group,the KYN content in the MG group was significantly lower(p<0.01),and the content in the ME group was further down-regulated than the MG group(p>0.05).Conclusion: Aerobic exercise can improve the depressive symptoms of chronic unpredictable stress depression mice model;aerobic exercise may regulate PGC-1α by regulating skeletal muscle miRNA-130 b,promote the expression level of KATs,and then regulate depression dogs The uric acid metabolism pathway achieves the effect of relieving depressive symptoms. |
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