基于~1HNMR代谢组学的抑郁症生物标志物发现及帕罗西汀干预作用

发布时间：2018-07-28 20:55

【摘要】：寻找抑郁症患者血清中潜在生物标志物,为抑郁症临床诊断及药物作用机制研究提供依据。筛选符合纳入标准的16例中重度抑郁症患者和16例健康人分别作为疾病组和对照组,其中疾病组抑郁症患者服用抗抑郁药物帕罗西汀两周。采集对照组、抑郁症患者以及抑郁症患者服用帕罗西汀两周后的血清进行1H NMR测试,采用代谢组学技术结合多元统计方法分析血清中内源性代谢产物的变化及其规律,发现具有显著性差异的代谢产物,结合相关代谢途径及受试者工作曲线(ROC)分析发现潜在生物标志物,并进一步探讨其与抑郁症的相关性及应用于临床诊断的可靠性和可行性。抑郁症患者血清中谷氨酸、谷氨酰胺、丙氨酸、N-乙酰糖蛋白、亮氨酸及异亮氨酸的水平显著升高,而葡萄糖水平显著降低(P0.05,P0.01),而帕罗西汀对丙氨酸、N-乙酰糖蛋白、异亮氨酸及葡萄糖代谢水平具有显著的回调作用(P0.05,P0.01),并调节谷氨酸、谷氨酰胺及异亮氨酸代谢水平使其具有向正常水平恢复的趋势,因此可被确定为潜在生物标志物。上述生物标志物的应用将有助于提高抑郁症临床诊断的客观性和抗抑郁药物临床疗效评价的准确性。
[Abstract]:To search for the potential biomarkers in the serum of depression patients and to provide evidence for the clinical diagnosis of depression and the mechanism of drug action. Sixteen patients with moderate and severe depression and 16 healthy persons were selected as disease group and control group respectively. Patients with depression in disease group were treated with paroxetine for two weeks. The serum of control group, patients with depression and patients with depression were tested for 1H NMR after taking paroxetine for two weeks. The changes and regularity of endogenous metabolites in serum were analyzed by metabolomics technique and multivariate statistical method. The potential biomarkers were found by (ROC) analysis of related metabolic pathways and operating curves of subjects. The relationship between the metabolites and depression and the reliability and feasibility of their application in clinical diagnosis were discussed. The levels of glutamate, glutamine, alanine N-acetylglycoprotein, leucine and isoleucine in the serum of patients with depression increased significantly, while the level of glucose decreased significantly (P0.05, P0.01). The metabolic level of isoleucine and glucose has a significant correction effect (P0.05, P0.01), and regulates the metabolism of glutamate, glutamine and isoleucine, so that it has a tendency to recover to normal level, so it can be identified as a potential biomarker. The application of these biomarkers will help to improve the objectivity of clinical diagnosis of depression and the accuracy of evaluation of clinical efficacy of antidepressants.
【作者单位】：山西大学中医药现代研究中心;山西大学化学化工学院;山西医科大学第一医院;
【基金】：国家自然科学基金资助项目(81173366;81441096)
【分类号】：R969

【相似文献】