Metabonomics Study On CSAP Treated By Acupuncturebased On Liquid Chromatography-mass Spectrometry

Objective: Under the circumstances of "precision medicine",to research the difference plama metabolites between chronic stable angina pectoris(CSAP)and healthy subjects,also to observe the effect of acupuncture on plasma metabolites in patients with CSAP,The results were analyzed by liquid chromatography-mass spectrometry(LC/MS).Methods: 1.Analysis of plasma metabolism in patients with CSAP: using LC/MS technique to analyze the difference of plasma metabolites between CSAP patients and healthy subjects,and to screen the key metabolites.2.Analysis of plasma metabolism in acupuncture treatment CSAP: using acupoint meridian and non-acupoint non-meridian two kinds of acupuncture intervention in patients with CSAP,to observe the effect of acupuncture on plasma metabolites in patients with CSAP and the metabolic differences between groups after acupuncture by LC/MS technology.3.Correlation analysis of differences metabolites and clinical indicators: Pearson correlation analysis will be the key to select metabolites with four weeks anginal pain,angina pain degree,6 minutes walking distance Test(6MWT),self-rating anxiety scale(SAS),self-rating depression scale(SDS),screening out the metabolites related to acupuncture treatment of CSAP,and find out the potential biomarkers of CSAP.Results:1.Study on the metabolic changes in the plasma of patients with CSAP.LC/MS technology has a good ability to distinguish between CSAP patients and healthy subjects plasma samples.Compared with the healthy control group,the difference of plasma m/z 301.2973(sphingosine)? 424.3419(linoleic acid,monoglyceride)were significantly increased in CSAP patients(P<0.05);281.2462(oleic acid,elaidic acid)?340.1395(tryptophan)? 229.1186(Leucyl-Aspartate,Hydroxyprolyl-Proline)were significantly lower than healthy control group(P<0.05).2.Study on the metabolic changes in the plasma of patients with CSAP treated by acupuncture.(1)Acupoint meridian and non-acupoint non-meridian can play a positive role in regulating the clinical symptoms of CSAP patients.However,the treatment effect of acupuncture group was better than that of non-acupoint non-meridian group,especially the number of angina pectoris and the degree of angina pectoris were most significant(P<0.05).(2)LC/MS technology has a good ability to distinguish between CSAP patients before and after acupuncture treatment and the difference between the two groups after acupuncture.The acupoint meridian group before and after acupuncture difference of m/z 146.0211(alpha ketoglutarate),98.0589(D-proline,L-proline)279.2343(linolenic acid)concentrations were increased significantly;317.1936(glucose: D-Linalool 3-glucoside,Neryl glucoside glucoside),406.2241(cyclophosphamide)concentrations were decreased significantly(P<0.05).The non-acupoint non-meridian group before and after acupuncture difference of m/z 304.1547(Resveratrol),407.2290(tryptophan derivatives: pyrifolidine)concentrations were increased significantly,409.2201(leukotriene B4)concentrations were decreased significantly(P < 0.05).Compared with the non-acupoint non-meridian group,acupoint meridian group after acupuncture difference of m/z 288.2011(arginyl-isoleucine,isoleucyl-arginine,arginyl-leucine,leucyl-arginine),279.2343(linolenic acid),257.0810(fatty acid ester)concentrations were increased significantly,444.3322(galactosylsphingosine,glucosyl sphingosine),406.2241(cyclophosphamide)concentration was decreased significantly(P<0.05).3.Study on the correlation between differential metabolites and clinical indexes.(1)Pearson linear correlation analysis was performed between plasma concentrations of CSAP patients at baseline and the frequency of angina pectoris,angina pectoris,6MWT,SAS and SDS,the result shows 376.3178(eicosapentaenoic acid),281.2462(oleic acid,elaidic acid)was significantly positively correlated with the number of angina pain per week;311.1224(ribonucleoside,uridine),424.3419(linoleic acid,monoglyceride)was significantly negative correlation with 6MWT;257.0810(fatty acid ester)was significantly positively correlated with SAS;340.1395(tryptophan),658.4056(phosphatidylserine)was significantly negatively correlated with SDS(P<0.05).(2)Pearson linear correlation analysis was performed between the changes of plasma metabolite concentration and the changes of angina pain frequency,the degree of angina pain,6MWT,SAS and SDS,the result shows 269.1350(muramic acid)was significantly negative correlation with changes in frequency of angina pectoris,627.4340(glyceride diester)was significantly negative correlation with 6MWT change value;285.1233(Lphenylalanyl-L-proline L)was significantly positively correlated with SAS change value;258.1092(Gamma-Glutamyl Glutamine)was significantly positively correlated with SDS change value(P<0.05).Conclusions: 1.The plasma metabolic profiles of CSAP patients were different from those of healthy control group,and the differences were mainly in the aspects of lipids,amino acids and carbohydrate metabolism.2.Acupoint meridian and non-acupoint non-meridian can improve the clinical symptoms of angina pectoris frequency every four weeks,degree of pain,anxiety and depression,And the effect of acupoint meridian was better than that of non-acupoint nonmeridian;Two ways can regulate the plasma metabolites of CSAP patients,but there are differences in the metabolites.3.The plasma metabolites of patients and acupuncture involved in the regulation of metabolic with four weeks of angina pain,degree of pain,Six minutes' Walk Test,anxiety,depression and other clinical symptoms are related.