Metabolomics Study On The Model Of Diabetic Rats Under Cold Dry Environment And Dietary Stress

Objective:The temperament disorder of cold-dry syndrome has regional characteristics.in terms of etiology research,its pathophysiological mechanism is remained unknown and there is no objective evaluation index in a rat model.Therefore,the purpose of this study is to investigate the evolution of the cold-dry syndrome with STZ induced type 2 diabetes mellitus(T2DM)rats and to confirm the feasibility of metabolic change in cold-dry syndrome and type 2 diabetes combination rat model.Methods:70male Sprague-Dawley(SD)rats were divided into the following three groups:the healthy control group,cold-dry syndrome group and cold-dry syndrome with T2DM group,T2DM group.After,all rat models were established,blood glucose was measured,then blood,urine samples and heart,kidney,liver,spleen,brain tissues were taken for experiment.Metabolic profiling was performed by ~1H-NMR spectroscopy,acquired data were used to proceed OPLS-DA and multivariate data analysis for differentiating the potential biomarkers.The constituent differences among the samples metabolite profiles of model groups were compared to control group respectively,statistical significantce(P<0.05).Results:Compared to the control group,the results showed in plasma,levels of metabolitessuchas3-hydroxybutyrate(3-HB),acetoacetate(Ace),proline(Pro),?-glucose(?-Glu),?-glucose(?-Glu)were significantly up-regulated,whereas the levels of leucine(Leu),valine(Val),lactate(Lac),alanine(Ala),pyruvate(Pyr),creatine(Cr),myo-inositol(Myo),were down-regulated in cold-dry syndrome with T2DM group;The results showed in urine,cold-dry syndrome with T2DM rats have significantly increased in taurine(Tau),?-Glu,?-Glu,Pro meanwhile decreased in Lac,Ala,acetate,glycoprotein,Pyr,2-ketoglutarate(2-KG),citrate(Ci),Cr,phenylalanine(Phe),phosphorylcholine(PC),1-methylhistidine,hippurate(Hip),creatinine(Cn),allantoin,urea,benzoate;The results showed in kidney,cold-dry syndrome with T2DM rats have significantly increased in3-HB,scyllo-inositol,?-Glu,?-Glu,Pro meanwhile decreased in Isoleucine(Ile),Leu,Val,Ala,lysine(Lys),acetate,methionine(Met),glutamate(Glu),glutamine(Gln),Pyr,aspartate(Asp),dimethylamine(DMA),Cr,ethanolamine,Tau,glycine(Gly),Threonine(Thr),Sarcosine(Sar),histidine(His),tyrosine(Tyr),choline(Cho),Phe;The results showed in liver tissues,cold-dry syndrome with T2DM rats have significantly increased in Myo,allantoin meanwhile decreased in Ile,Leu,Val,Lac,Ala,Pyr,Lys,acetate,Glu,Gln,glutathione,Sar,Cho;The results showed in brain tissues,cold-dry syndrome with T2DM rats have significantly increased in Lac,Cr,scyllo-inositol,?-Glu meanwhile decreased in Leu,Ile Val,Ala,Glu,Met,GABA,Cho,Pyr,Thr,Tyr,His,Cn;The results showed in spleen tissues,cold-dry syndrome with T2DM rats have significantly increased in 3-HB,Tau,scyllo-inositol,?-Glu,Pro,?-Glu meanwhile decreased in Leu,Ile,Ala,Lys,Gln,Met,Glu,carnitine,methylamine,glutathione,Cho,Thr;The results showed in heart tissues,cold-dry syndrome with T2DM rats have significantly increased in 3-HB,scyllo-inositol,?-Glu,Myo,?-Glu,allantoin meanwhile decreased in Leu,Ile,Val,isobutyric acid,Lac,acetate,Gln,Lys,Cr,PC,Tau,Thr.Conclusion:The main difference between cold-dry syndrome with type 2 diabetes and type 2 diabetes in western medicine is in liver metabolism,In cold-dry syndrome with T2DM group,underutilization of hepatic sugar results in the decrease of amino acid synthesis and the inhibition of fatty acid oxidation.However,in type 2 diabetes mellitus may occur the over-utilization of hepatic sugar and the enhancement of fatty acid oxidation.