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The Characteristics Of Metabonomics And The Change After Drug And Intervention Therapy In Patients With Unstable Angina Pectoris

Posted on:2017-04-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:W YaoFull Text:PDF
GTID:1224330509462337Subject:Internal Medicine
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Objective: In our study, ~1H-NMR technology was used to find the characteristic of metabolomics in patients with unstable angina pectoris, look for related metabolic markers, and compare the change of metabolomics after intervention and drug treatment.Methods: The survey was performed between Janyary 2015 to June 2015 in Tianjin Medical University General Hospital. The patients were grouped according to the result of selective coronary angiography. Unstable angina pectoris group for at least a degree of coronary artery stenosis greater than 75%, and suffered coronary artery stent implantation; control group where no more than 50% of coronary artery stenosis. Serum samples for ~1H-NMR metabolomics were frozened and storaged at ultra-low temperatures. There were 101 patients in Unstable angina pectoris group and 132 individuals in control group. Patients in unstable angina pectoris group were given standard drug treatment and follow-up. After an average follow-up of 3.3 months, blood lipids were detected. If the LDL-C dropped to 1.8mmol/L or declin more than 50% compared to the baseline, these patients were defined as after-treatment group. Serum samples of after-treatment group were frozened and storaged at ultra-low temperatures. Agilent 600 MHZ DD2 NMR spectrometer was used to test the serum samples between unstable angina pectoris group and control group, unstable angina pectoris group and after-treatment group. PCA, PLS-DA, OPLS-DA analysis methods were used to analyze the differences of metabonomics between these groups.Results: Combination of orthogonal signal correction PLS method and ~1H-NMR technology efficiently identified the differences among the serum metabolic groups and significantly improved the data resolution. The high accuracy and predictability of the OPLS-DA classification modal is demonstrated by a variety of authentication methods. Many substances were significantly different between unstable angina pectoris group and non-CHD group, included LDL, glycerolphosphocholine, threonine, phosphocholine, HDL, 3-Hydroxybutyrate, 1-Methylhistidine, lipid, phenylalanine, glutamate, glutamine, creatine, lysine, choline, Leucine, Valine, myo-Inositol, Isoleucine, VLDL, lactate, trimethylamine N-oxide. Glucose, lipid,protein and nucleic acid metabolism disorders were existed in patients with unstable angina pectoris. The different substances between unstable angina pectoris group and after-treatment group were lipid, lysine, dimethylaimine, 1-Methylhistidine, LDL, tyrosine, sarcosine. The different substances between non-CHD group and after-treatment group were leucine, valine, lipid, lysine, creatine, lactate, alanine, phenylalanine, glutamate, glutamine, phosphocholine, glycine, isoleucine, tyrosine, choline, threonine.Conclusion: ~1H-NMR metabonomics method was simple, economic and effective. This method could filter out patients with unstable angina, and could evaluate the effectiveness of drug treatment. It could explore the molecular mechanism of unstable angina pectoris and provide a clue to discover new therapeutic targets.
Keywords/Search Tags:~1H-NMR, metabonomics, unstable angina pectoris, medicine and intervention treatment, differences metabolites
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