Study On Protective Effect And Metabolomics Of Ethanol Extract Of Propolis On Isoprenaline-induced Acute Myocardial Ischemia In Mice

The protective effect of the ethanol extract of propolis(EEP)on isoprenaline(ISO)-induced acute myocardial ischemia in mice was studied in this research,as well as its metabolomics.The results of present study were described as follow:1.After mice injected different doses of ISO for 2 day,the changes of their behaviors,electrocardiograms and serum metabolites were observed to explore the optimal preparation conditions of ISO-induced acute myocardial ischemia in mice.The model mice were intraperitoneally injected ISO 6.0 mg/kg for 2 days have typical myocardial ischemia characteristics,such as the ECG ST-segment and T-wave shift values,and heart rates increased.Therefore,the level of cardiac troponin T(cTn-T),lactate dehydrogenation(LDH)and creatineg kinase isoenzyme(CK-MB)were significantly increased in the serum.Meanwhile,the content of Endothelin-1(ET-1)and B-type brain natriuretic peptide(BNP)were not significantly increased,suggesting little possibility of heart failure in some time.The myocardial ischemia induced by this method could be improved by positive drugs and the body's own repairment.In conclution,The tested mice can successfully replicate myocardial ischemia for the further research.2.To investigate the protective effects and mechanism of EEP on ISO-induced acute myocardial ischemia injury in tested mice.The acute myocardial ischemia model in the mice was induced by ISO(6.0 mg/kg)intraperitoneal injection for 2 days.The survival time of myocardial ischemia mice under oxygen deficiency,ECG S-T section and heart index was observed,and the level of LDH,CK-MB,malondialdehyde(MDA)and superoxide dismutase(SOD)in serum were determined,The whole blood viscosity and RBC aggregation index were measured.2,3,5-Triphenyltetrazolium chloride(TTC)staining was used to determine focal myocardial ischemia.Compared with model group,EP treatment could significantly prolong the survival time,decrease S-T section change,heart index and the level of LDH and CK-MB,as well as increase SOD activity and reduce MDA content,reduce whole blood viscosity and erythrocyte aggregation at different shear rate(P<0.05).EEP has protective effect on ISO-induced acute myocardial ischemia in mice,with improving oxidation stress reaction,blood viscosity and erythrocyteaggregation.3.The metabolics study of EEP on ISO-induced acute myocardial ischemia in mice were investigated,the endogenous metabolites in serum of the normal group,the acute myocardial ischemia model group and the propolis group were analyzed by gas chromatography-mass spectrometry.As a result,a total of 49 metabolites were identified in the serum sample.The metabolite information amonge the normal group,acute myocardial ischemia model group and propolis group could be discriminated by PLS-DA analysis.The relevant biomarkers were as follows:butanoic acid,glucopyranose,palmitelaidic acid,galactose,tetradecanoic acid,turanose,oleic acid,hexadecanoic acid,L-threonine,inositol,L-proline,propanoic acid,heptadecanoic acid,arachidonic acid,ethanedioic acid,2,3,4-trihydroxybutyric acid,9,12-octadecadienoic acid,urea and erucylamide.The results indicated that the protective effect of EEP on ISO-induced acute myocardial ischemia in mice was related to different metabolic pathways,such as fatty acid metabolism,glucose metabolism and amino acid metabolism.