| ObjectiveTo analyze the changes of metabolites in hypothalamus of IA model rats by metabolomics techniques and methods.The biological nature of IA was analyzed from the perspective of metabolomics.To observe the regulation of Xiao’er Kaiwei Zengshi Mixture to the metabolites in hypothalamus of IA model rat and to explore the specific treatment mechanism of Xiao’er Kaiwei Zengshi Mixture on IA.Methods120 SD rats were randomly divided into 20 blank rats and 100 model rats.IA model was prepared by special high fat diet feeding.After successful modeling,the model group was randomly divided into 5 groups,each group consised of 20 model rats: respectively,the model group,Xiao’er Kaiwei Zengshi Mixture high,medium and low dose groups and Jianweixiaoshi tablets group;After 15 days of drug intervention,the rats were executed and the hypothalamic tissue was taken to prepare experimental samples.Hypothalamic tissue samples were detected by liquid chromatography-mass spectrometry(LC-MS)metabolomics technique,and the detected data were analyzed by multivariate statistical methods.Finding the differential metabolites in hypothalamic tissue and analyzing the relevant metabolic pathways using variable importance projection value(threshold >1)of orthogonal importance least squares discriminant analysis(OPLS-DA)and the P value(P<0.05)of t-test.Results1.The daily intake of model group rats was 40-60 % lower than that in blank group since the 28 th day,which was significantly lower than that in blank group(P<0.05).The food intake of treatment group was significantly improved compared with model group(P<0.05).The body weight of model group was 10-15 % lower than that of blank group since the 7th day,which was significantly lower than that of blank group(P<0.05).The weight of the treatment group was significantly improved compared with the model group,especially in the high dose group.2.From the total PCA scores map,it can be seen that the six groups of samples are clearly separated,and each group shows obvious clustering trend.At the same time,it can beseen that each treatment group has a tendency to return to the normal group,and the high dose group is the closest to blank group,indicating that the treatment of the high dose group was the best.3.Through the identification and analysis of metabolites produced by hypothalamic tissue in IA model rats,30 different metabolites such as pantothenic acid,LysoPC(14:0),LysoPC(14:1(9Z)),thioglycolic acid,hypoxanthine,inosine,xanthine,guanosine,sphingosine,phytosphingosine,pyroglutamic acid,glutathione,and oxidized glutathione were found.4.The differential metabolites involved a total of 28 metabolic pathways,of which the top five metabolic pathways with effect values greater than 0.1 were biosynthesis of phenylalanine/tyrosine and tryptophan,glutathione metabolism,taurine and Metataurine metabolism,phenylalanine metabolism,pantothenic acid and coenzyme A biosynthesis.Conclusion1.After the treatment with Xiao’er Kaiwei Zengshi Mixture,body weight and food intake of IA model rats were significantly increased compared with model group,the content of differential metabolites was closer to blank group than model group.It is confirmed that Xiaoer Kaiwei Zengshi Mixture has a relatively specific therapeutic effect on IA,can improve food intake and weight,and regulate metabolic pathways of disorders.2.Potential biomarkers of anorexia such as LysoPC(16:1(9Z)),LysoPC(14:1(9Z)),oxidized glutathione,reduced glutathione,ornithine,histidine,citrulline,sphingosine,inosine,guanosine,L-leucine,palmitic acid,etc.were found in the reserch.It reveals that the occurrence of anorexia was related to metabolic disorders such as the biosynthesis of phenylalanine/tyrosine and tryptophan,glutathione metabolism,taurine and hypotaurine metabolism,phenylalanine metabolism,pantothenic acid and coenzyme A biosynthesis.3.Xiao’er Kaiwei Zengshi Mixture can regulate the metabolic pathways related to disorders,which may be one of the mechanisms of Xiaoer Kaiwei Zengshi Mixture in the treatment of IA. |
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