A Preliminary Assessment On Anti-depressive Effect Of Polyrhachis Vicina Roger And Study On Mechanisms Of Alcoholic Gastric Injury Base On Metabonomics

Objective:(1)Based on 1H nuclear magnetic resonance(1H-NMR)metabolomics,to search for potential differential metabolites in ovariectomized(OVX)rats brain tissue and identified their metabolic pathways,and preliminarily assessing the improved effects of ethyl alcohol extract of Polyrhachis vicina Roger(EAPR)on depressive-like behavior in OVX rats.From the metabolic level,the anti-depressive effect and metabolic regulation function of eapr were preliminarily revealed,which to provide a reference for future research.(2)To find out the potential differential metabolites in rat gastric tissue of alcoholic gastric injury,and to determine the related metabolic pathways through 1H-NMR metabolomics.To preliminary investigate the pathological mechanism of alcoholic gastric injury in rats.Methods:(1)After one month of adaptive feeding,the SD rats(female,n=48)were randomly divided into six groups(n=8):Normal control group(Normal),Ovariectomized model control group(OVX),OVX+Low dose EAPR(EAPR-L,100mg/kg),OVX+Middle dose EAPR(EAPR-M,200 mg/kg),OVX+High dose EAPR(EAPR-H,400mg/kg)and OVX+Positive control Estradiol Valerate Tabletes group(Positive control,0.1mg/kg).After administration,the rats were tested for sucrose preference test and forced swimming test and were sacrificed after the behavior experiment.The brain tissue were taken for 1H-NMR metabolomics research,and the NMR data were analyzed by PC A,PLS-DA and OPLS-DA pattern recognition analysis methods.Then,combined with HMDB database,literature and other resources,screening and identifying the significant different metabolites in brain tissue between the Normal control group and OVX group,which to explore of EAPR improve the depressive symptoms of OVX rats metabolomics mechanism.(2)After one week of adaptive feeding,the SD rats(male,n=12)were randomly divided into Normal control group(Normal,n=6)and alcohol model group(Model,n=6).Fasting 12 h(drinking freely),alcohol model group rats were intragastric administration 7 g/kg body weight 30%(v/v)alcohol,whereas the Normal control group rats were given the same volume of normal saline,once a day for seven days.After the last administration,all rats were killed after fasting 12 h(drinking freely).The gastric tissue were taken immediately for 1 H-NMR metabolomics research,and data processing such as PCA,PLS-DA and OPLS-DA pattern recognition analysis was carried out.Results:(1)Compared with Normal group,depression-like behaviors such as anhedonia and desperation were found in OVX group,which showed decrease significantly of sucrose preference index(P<0.05),the immobility time of forced swimming test increased significantly(P<0.05).After administration,compared with the OVX group,the sucrose preference index was significantly increased and the immobility time was significantly shortened(P<0.05)in the EAPR-H and EAPR-M groups,showing a tendency to return to Normal control group levels.Brain tissue 1H-NMR metabonomics analysis showed that a total of nine metabolites with significant changes were identified in Normal control group and OVX group.Compared with Normal control group,the level of isoleucine,glycine,myo-inositol were markedly up-regulated,while the glycerophosphocholine aspartic acid,N-acetyl-L-aspartic acid,adenosine,inosine,niacinamide level were markedly down-regulated in OVX group.Analysis of metabolic pathways showed that these nine differential metabolites were involved in amino acid metabolism,energy metabolism,niacinamide metabolism,glycerophospholipid metabolism and inositol metabolism,respectively.After administration,compared with the OVX group,the eapr could significantly reverse the other seven metabolites except glycine and myo-inositol,showed a tendency to return to the Normal control group,while these seven differential metabolites are involved in amino acid metabolism,energy metabolism,nicotinamide metabolism and glycerophospholipid metabolism pathways,respectively.(2)Gastric tissue 1H-NMR metabonomics analysis showed that a total of thirteen metabolites with significant changes were identified in Normal control group and alcohol model group.Compared with the Normal control group,the contents of glycerol,choline,betaine,glucose,sucrose,adenosine,inosine,serine,leucine and proline were markedly elevated,whlie the glutamine,taurine and 4-hydroxyproline were significantly decreased in the alcohol model group.Metabolic pathway analysis revealed that these metabolites were involved in metabolic pathways such as oxidative stress,cell metabolism,glycometabolism,energy metabolism,purine metabolism,taurine metabolism,respectively.Conclusions:(1)OVX can induce depressive-like behavior and several metabolic pathways disorder in brain tissue of rats.EAPR can obviously attenuates depression-like behavior in OVX rats,its anti-depressant mechanism may be closely related to the regulation of amino acid metabolism,energy metabolism,niacinamide metabolismand glycerophospholipid metabolism pathways,thereby reducing depression symptoms in brain tissue of OVX rats.In this study,the EAPR has anti-depressant activity and metabolic regulation function were preliminarily revealed from the metabolic level(2)These thirteen identified differentially metabolites in gastric tissue may be used as candidate biomarkers for alcoholic gastric injury in rats.The effect of alcoholic gastric mucosal injury in rats is closely related to the metabolic disturbance of oxidative stress,cell metabolism,glucose metabolism,energy metabolism,purine metabolism,taurine metabolism in gastric tissues.