本文選題：氫離子核磁共振 + 代謝組學　； 參考：《天津醫(yī)科大學》2016年博士論文

【摘要】：目的:應(yīng)用氫離子核磁共振(1H-NMR)代謝組學方法,觀察不穩(wěn)定型心絞痛(UAP)患者血清代謝組學變化特點,尋找與UAP患者相關(guān)的代謝標記物,并比較UAP患者經(jīng)介入及藥物治療后的代謝組學變化情況。方法:選擇2015年1月至2015年6月天津醫(yī)科大學總醫(yī)院心內(nèi)科以UAP入院的患者為研究人群,根據(jù)冠狀動脈造影(CAG)結(jié)果進行分組,UAP組為至少一只冠狀動脈主干狹窄程度大于75%的患者,并行經(jīng)皮冠狀動脈支架植入術(shù);對照組為冠狀動脈狹窄未超過50%者。兩組均行血常規(guī)及生化檢查,并留取血清樣本,低溫凍存。UAP組101人,對照組132人。對UAP組患者規(guī)范藥物治療并隨訪,平均隨訪3.3±0.4個月,選擇低密度脂蛋白膽固醇(LDL-C)下降至1.8mmol/L或下降幅度超過50%的患者定義為治療后組,留取血清樣本,低溫凍存。隨機選取UAP組、對照組及治療后組患者各22例,應(yīng)用Agilent DD2 600MHz NMR譜儀,采用代謝組學1H-NMR技術(shù)檢測三組血清樣本。應(yīng)用主成分分析(PCA)、偏最小二乘法判別分析(PLS-DA)、正交矯正偏最小二乘法判別分析(OPLS-DA)分別對UAP組與對照組、UAP組與治療后組及對照組與治療后組代謝組學檢測結(jié)果進行分析比較,篩選組間差異代謝物。結(jié)果:(1)1H-NMR檢測和分析方法診斷UAP模型的解釋度和預(yù)測度分別為89.4%和87.7%。模型中UAP組與對照組相比的差異代謝物,按相關(guān)性強弱排序包括:LDL↑、甘油磷酸膽堿↓、蘇氨酸↓、磷酸膽堿↓、HDL↓、3-羥基丁酸↑、1-甲基組氨酸↓、脂類↑、苯丙氨酸↓、谷氨酸↓、肌酸↓、賴氨酸↓、谷氨酰胺↓、膽堿↓、亮氨酸↓、纈氨酸↓、肌醇↑、異亮氨酸↓、VLDL↑、乳酸↑、氧化三甲胺↑。(2)UAP組治療后與治療前及對照組比較同樣存在多種代謝物變化,主要集中于能量代謝、氨基酸代謝、脂代謝等方面。治療后組與UAP組比較血清脂類↓、賴氨酸↑、二甲胺↑、1-甲基組氨酸↑、LDL↓,酪氨酸↑和肌氨酸↑。治療后組與對照組比較血清亮氨酸↓、纈氨酸↓、脂類↓、賴氨酸↓、肌酸↓、乳酸↑、丙氨酸↓、苯丙氨酸↓、谷氨酰胺↓、磷酸膽堿↓、甘氨酸↓、異亮氨酸↓、谷氨酸↓、酪氨酸↑、膽堿↓和蘇氨酸↓。結(jié)論:(1)1H-NMR檢測和分析方法在診斷UAP方面的可靠性高,為今后豐富UAP的診斷方法打下基礎(chǔ)。(2)UAP患者血清中多種代謝物發(fā)生變化,主要涉及能量代謝、氨基酸代謝、脂代謝等多個方面。心肌的代謝是一個十分復(fù)雜的過程,許多機制仍不清楚。今后我們可以進一步分析1H-NMR檢測和分析方法得到的差異代謝物,為發(fā)現(xiàn)新的治療靶點提供線索。
[Abstract]:Objective: to observe the changes of serum metabonomics in patients with unstable angina pectoris (UAP) by hydrogen ion nuclear magnetic resonance (1H-NMR) metabolomics, and to search for the metabolic markers related to UAP patients. The metabonomics changes of UAP patients after intervention and drug therapy were compared. Methods: from January 2015 to June 2015, patients admitted to UAP in Department of Cardiology, Tianjin Medical University General Hospital, were selected as the study group. According to the results of coronary angiography (CAG), the UAP group was divided into two groups: the patients with at least one coronary artery stenosis more than 75%, and the control group with coronary artery stenosis less than 50%. Blood routine examination and biochemical examination were performed in both groups, and serum samples were collected, 101 in cryopreservation group and 132 in control group. The patients in UAP group were treated with standard drug therapy and followed up. The average follow-up was 3.3 鹵0.4 months. The patients with low density lipoprotein cholesterol (LDL-C) decreased to 1.8 mmol / L or more than 50% were defined as the group after treatment. Serum samples were collected and cryopreserved. 22 patients in UAP group, 22 patients in control group and 22 patients in post-treatment group were randomly selected. The serum samples of three groups were detected by using Agilent DD2600MHz NMR spectrometer and metabolomics 1H-NMR technique. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal correction partial least squares discriminant analysis (OPLS-DA) were used to analyze and compare the results of metabolism in UAP group and control group. Different metabolites were screened among groups. Results: (1) the interpretation and prediction of 1H-NMR were 89.4% and 87.7%, respectively. The different metabolites of UAP group compared with the control group in order of correlation include: LDL, glycerol choline phosphate, threonine, choline phosphate, HDL-C 3-hydroxybutyrate 1-methylhistidine, lipids, phenylalanine. Glutamate, creatine, lysine, glutamine, choline, leucine, valine, inositol, isleucine, VLDL, lactic acid, (2) the changes of metabolites in UAP group were similar to those before treatment and control group, mainly in energy metabolism, amino acid metabolism, lipid metabolism and so on. After treatment, serum lipids, lysine, dimethylamine 1-methylhistidine, tyrosine and sarcosine were compared between the treatment group and the UAP group. After treatment, serum leucine, valine, lipids, lysine, creatine, lactate, alanine, phenylalanine, glutamine, choline phosphate, glycine, isoleucine were compared between the treatment group and the control group. Glutamate, tyrosine, choline and threonine. Conclusion: (1) the method of 1H-NMR is reliable in the diagnosis of UAP, which lays a foundation for the diagnosis of UAP in the future. (2) the changes of many metabolites in the serum of UAP patients are mainly involved in energy metabolism, amino acid metabolism, lipid metabolism and so on. Myocardial metabolism is a complex process, and many mechanisms remain unclear. In the future, we can further analyze the differential metabolites obtained by 1H-NMR detection and analysis, and provide clues for the discovery of new therapeutic targets.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R541.4

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