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A Metabonomics Research On The Myocardial Protective Effect Of Ginsenoside Rb1 Treated Diabetic Rats

Posted on:2018-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:B PangFull Text:PDF
GTID:1314330515476103Subject:Internal Medicine
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Background:Diabetes mellitus is one of the most common chronic diseases in humans.Diabetes has many kinds of complications,such as diabetic nephropathy and retinopathy,and diabetic foot,and the most serious one is the cardiovascular system.Diabetic cardiomyopathy(DCM)is to exclude myocardial injury caused by coronary heart disease,heart failure,high blood pressure and other known diseases.Many factors involved to induce DCM: such as hyperglycemia,fatty acid metabolism disorders,activation of the RAAS system,and mitochondrial metabolism,increased oxidative stress,glycosylation end products increase,and so on.Ginseng saponin is the main biologically active components of ginseng.People haved found about 30 kinds of saponin monomer.Ginsenoside Rb1 is considered to have important effects.Its main function includes the effects of anti-tumor,the regulation of blood sugar,inhibition of cell apoptosis and so on.People found that there is a strong antioxidant activity in ischemic injury and endothelial cells later.But if the Rb1 has a protective effect on diabetic cardiomyopathy and its mechanism is not yet clear.Metabolomics is defined as a quantitative measurement of multi-parametric metabolic responses of multi-cellular systems to pathophysiological stimuli or genetic signaling.The applications of metabolomics in studying the effects and mechanisms of drugs on diseases have been adopted.Objective:1.To study the mechanism of DCM based on the applications of metabolomics.2.To study the protective effect of ginsenoside Rb1 on DCM and its mechanism based on Rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry(RRLC-QTOF/MS).3.To study the clinical applications of metabolomics.A Metabonomics Study of Chronic Heart Failure and Atherosclerosis was used to find the differential biomarkers.Methods:To establish DM rat models by high fat and sugar feed add intraperitoneal injection streptozotocin.we observe rats’ weight,serum glucose,triglycerides.We use HE staining,Masson staining and electron microscopy to observe myocardial morphological changes.Application of metabolomics methods by RRLC-QTOF/MS is used to find the function of Rb1 on DCM.A Metabonomics Study base on RRLC-QTOF/MS of Chronic Heart Failure and Atherosclerosis was used to find the differential biomarkers.Results:1.Ginsenoside Rb1 two groups decrease level of diabetic rats serum glucose,lipids,enzymes.2.Ginsenoside Rb1 two treatment groups could improve myocardial ultrastructural damage and myocardial fibrosis.3.A total of eleven significantly changed metabolites had been found by RRLC-QTOF/MS and identified as potential biomarkers,which may play an important role in the mechanism of DCM.4.A total of six significantly changed metabolites had been found byRRLC-QTOF/MS and identified as potential biomarkers,which may explain the function of Ginsenoside Rb1.5.A total of two significantly changed metabolites had been found by RRLC-QTOF/MS and identified as potential biomarkers of CHF.6.A total of two significantly changed metabolites had been found by RRLC-QTOF/MS and identified as potential biomarkers of AS.Conclusions:1.Ginsenoside Rb1 can reduce myocardial ultrastructure damage and improve the metabolic disorders.2.Ginsenoside Rb1 may play a protective role of amino acid metabolism,energy metabolism,pyrimidine metabolism and gut flora metabolism.3.Uracil metabolism and Tryptophan metabolism may play an important role in the mechanism of CHF based on RRLC-QTOF/MS.4.Purine metabolism and Amino acid metabolism may play an important role in the mechanism of AS based on RRLC-QTOF/MS.Innovation:1.In this study,Ginsenoside Rb1 intervention STZ-induced diabetic rats,we can observe the protective effect on diabetic cardiomyopathy.2.In this study,we find the biomarkers of DCM by RRLC-QTOF/MS,that may supply some evidence to explore the mechanism of DCM.3.In this study,we find the targets of Ginsenoside Rb1 on diabetic cardiomyopathy by RRLC-QTOF/MS,that supply a new method to study mechanism of traditional chinese medicine.4.In this study,we study the mechanism of CHF and AS by RRLC-QTOF/MS.
Keywords/Search Tags:Ginsenoside Rb1, Diabetic cardiomyopathy, Metabonomics, Heart failure, Atherosclerosis
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