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Metabolomics Approaches For Rats With Acute Myocardial Infarction And Chronic Heart Failure

Posted on:2016-11-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:F YangFull Text:PDF
GTID:1364330566991736Subject:Department of Cardiothoracic Surgery
Abstract/Summary:PDF Full Text Request
Objective Aim of the study is going to investigate and analyze the serum and myocardium of rats with acute myocardial infarction or chronic heart failure via the metabonomic technique.Build the model distinguishing disease.Explore micromolecule metabolites associated with development and progression of diseases based on the data and combing the network database.Search the pathological mechanisms for acute myocardial infarction and chronic heart failure from the view of metabolism.Methods 1.Using USB digital visual endoscopy improves the method of modeling endotracheal intubation during myocardial infarction.2.Establish myocardial infarction model by ligaturing coronary artery and collect the sample of serum and myocardium after AMI 1h and 1w.Verify the model through the mean of HE staining and ultrasonic cardiogram.3.Build the model of CHF through abdominal aortic coarctation and collect the myocardium.Check the model via HE staining and ultrasonic cardiogram.4.Analyze the serum and myocardium of rats with acute myocardial infarction and chronic heart failure at different times through Accela ultra high performance liquid chromatography(HPLC)system with LTQ Orbitrap XL mass spectrometry produced by the Thermo Company.Processing and filtering the data via Mzmine 2.0 software.Through PCA(principal component analysis)and OPLS-DA(orthogonal partial least squares discriminant analysis)of SIMCA-P,the disease distinguishing model was established.After that,non parameter test were used to select feature metabolites which can separate normal,AMI,CHF group,and these ions were then identified and assigned to corresponding metabolite.Results 1.The success rate of intubation can be increased obviously by using USB digital visual endoscopy,reducing intubation complications.2.The myocardial infarction model were constructed successfully,five of control group all survived,5of AMI 1 h group all survived,7 in 10 of myocardial infarction survived.HE staining showed inflammatory cell infiltration and myocyte swelling and necrosis in AMI 1 h group.In contrast,more severe infiltration of inflammatory cells and fibroblasts as well as decreased myoctyes in infracted area were observed in 1-week group animals.Ultrasound examination demonstrated that the heart function was badly impaired in1-week group with lowered ejection fraction and fractional shortening when compared with other groups.3.We established a rat model of CHF.All animals(including 5 normal control,5 sham operated,and 10 abdominal aortic coarctation)survived.H & E staining of myocardial tissue demonstrated that the number of myocyte was significantly reduced in CHF group than that in other groups.What's more,myocardial hypertrophy was easily identified in CHF group.Ultrasound examination revealed a decreased heart function(including ejection fraction and fractional shortening)of mice in CHF group compared with control groups.4.We established serum and tissue model of AMI at different time periods and tissue model of CHF in rats.There is no different in 1 h group and sham group.9 metabolites were verified in 1 w group,most of them were LPE.13 irons were certified in myocardial hypertrophy.Concluion1.The success rate of intubation can be increased obviously by using USB digital visual endoscopy,reducing intubation complications.2.Using high performance liquid chromatography and mass spectrometry platform found significant differences of small molecule metabolites has better ability to distinguish between acute myocardial infarction and healthy rats,and can be used as a potential diagnostic markers and new therapeutic targets to do further research in the field of basic science.3.Metabonomics platforms used to detect the related characteristics of metabolites,and heart failure in heart failure and the control group differences between the main metabolites of free fatty acid,succinic acid,creatine,branched chain amino acids and other substances.
Keywords/Search Tags:Metabolomics, AMI, CHF, UPLC/MS
PDF Full Text Request
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