不稳定型心绞痛患者代谢组学变化特点及治疗前后的对照研究

发布时间：2018-07-12 13:17

本文选题：氢离子核磁共振 + 代谢组学　；参考：《天津医科大学》2016年博士论文

【摘要】：目的:应用氢离子核磁共振(1H-NMR)代谢组学方法,观察不稳定型心绞痛(UAP)患者血清代谢组学变化特点,寻找与UAP患者相关的代谢标记物,并比较UAP患者经介入及药物治疗后的代谢组学变化情况。方法:选择2015年1月至2015年6月天津医科大学总医院心内科以UAP入院的患者为研究人群,根据冠状动脉造影(CAG)结果进行分组,UAP组为至少一只冠状动脉主干狭窄程度大于75%的患者,并行经皮冠状动脉支架植入术;对照组为冠状动脉狭窄未超过50%者。两组均行血常规及生化检查,并留取血清样本,低温冻存。UAP组101人,对照组132人。对UAP组患者规范药物治疗并随访,平均随访3.3±0.4个月,选择低密度脂蛋白胆固醇(LDL-C)下降至1.8mmol/L或下降幅度超过50%的患者定义为治疗后组,留取血清样本,低温冻存。随机选取UAP组、对照组及治疗后组患者各22例,应用Agilent DD2 600MHz NMR谱仪,采用代谢组学1H-NMR技术检测三组血清样本。应用主成分分析(PCA)、偏最小二乘法判别分析(PLS-DA)、正交矫正偏最小二乘法判别分析(OPLS-DA)分别对UAP组与对照组、UAP组与治疗后组及对照组与治疗后组代谢组学检测结果进行分析比较,筛选组间差异代谢物。结果:(1)1H-NMR检测和分析方法诊断UAP模型的解释度和预测度分别为89.4%和87.7%。模型中UAP组与对照组相比的差异代谢物,按相关性强弱排序包括:LDL↑、甘油磷酸胆碱↓、苏氨酸↓、磷酸胆碱↓、HDL↓、3-羟基丁酸↑、1-甲基组氨酸↓、脂类↑、苯丙氨酸↓、谷氨酸↓、肌酸↓、赖氨酸↓、谷氨酰胺↓、胆碱↓、亮氨酸↓、缬氨酸↓、肌醇↑、异亮氨酸↓、VLDL↑、乳酸↑、氧化三甲胺↑。(2)UAP组治疗后与治疗前及对照组比较同样存在多种代谢物变化,主要集中于能量代谢、氨基酸代谢、脂代谢等方面。治疗后组与UAP组比较血清脂类↓、赖氨酸↑、二甲胺↑、1-甲基组氨酸↑、LDL↓,酪氨酸↑和肌氨酸↑。治疗后组与对照组比较血清亮氨酸↓、缬氨酸↓、脂类↓、赖氨酸↓、肌酸↓、乳酸↑、丙氨酸↓、苯丙氨酸↓、谷氨酰胺↓、磷酸胆碱↓、甘氨酸↓、异亮氨酸↓、谷氨酸↓、酪氨酸↑、胆碱↓和苏氨酸↓。结论:(1)1H-NMR检测和分析方法在诊断UAP方面的可靠性高,为今后丰富UAP的诊断方法打下基础。(2)UAP患者血清中多种代谢物发生变化,主要涉及能量代谢、氨基酸代谢、脂代谢等多个方面。心肌的代谢是一个十分复杂的过程,许多机制仍不清楚。今后我们可以进一步分析1H-NMR检测和分析方法得到的差异代谢物,为发现新的治疗靶点提供线索。
[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 卤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.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4

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