Study On The Metabolic Profile Of Stable Angina Pectoris With Cold Coagulation And Qi Stagnation And The Therapeutic Mechanism Of Shexiang Baoxin Pill

Objective To reveal the metabolic profile of stable angina pectoris(SAP)and its subtypes,and obtain diagnostic biomarkers of disease and syndrome.Meanwhile,the underlying metabolic mechanisms of patients with SAP and acute myocardial infarction(AMI)rats treated by Shexiang Baoxin pill(SBP)were studied.MethodsMulti-platform metabolomics were performed on serum samples of 135 SAP patients and 30 healthy controls(HC),then multivariate and univariate statistical analyses were performed to screen differential metabolites and draw differential metabolic pathways.Random forest and ROC diagnostic models were applied to obtain “disease-syndrome”diagnostic biomarkers.Further absolute quantitative analysis of 306 metabolites obtains reliable differential metabolites,metabolic pathways,and “disease-syndrome”biomarkers.Using the same method,we also analyzed the serum of 44 patients with cold coagulation and qi stagnation(CCQS)before and after the intervention of SBP.We obtained the differential metabolites and metabolic pathways,as well as potential diagnostic biomarkers that could evaluate the therapeutic effect of SBP.To further study the metabolic mechanism of SBP,the AMI rat model was generated by ligating the coronary artery.After two weeks of treatment with SBP,myocardial enzyme,and echocardiography index were performed for a therapeutic evaluation.The metabolic profiles of different groups in different biological samples(heart tissue,serum,urine,and feces)were analyzed by LC-MS metabolomics.ResultsA list of differential metabolites including phospholipids,fatty acids,amino acids,organic acids,bile acids were identified.Compared with HC,these metabolites and metabolic pathways showed significant changes in SAP patients and its subtypes(CCS and syndrome classification).The potential biomarkers panel(oxalic acid,ketoglutaric acid and pyruvic acid)exhibited an excellent diagnostic performance in distinguishing SAP patients from HC(AUC = 0.913).In addition,the biomarkers panel of different“diseases-syndromes” also exhibited good diagnostic performance in distinguish different CCS and syndrome subtypes.After two weeks of SBP intervention,the metabolic profile of CCQS patients and AMI rats had significant metabolic changes,mainly including glycerolphospholipids,amino acids,fatty acids,and their metabolic pathways.Meanwhile,SBP intervention can significantly reverse the syndrome biomarkers returned to the level of HC.ConclusionThe above studies revealed that SAP patients had extensive metabolic dysregulation,and for the first time,revealed the metabolic characteristics of SAP patients at different stages based on CCS classification.We further obtained another subtype of SAP,which is significantly associated with the history of angina pectoris.At the same time,we also revealed the metabolic characteristics and syndrome biomarkers of SAP patients with CCQS,and SBP can restore most of the syndrome biomarkers to the level of HC.The therapeutic effect of SBP on patients and rats is associated with improved metabolic dysregulation.