【摘要】：尋找抑郁癥患者血清中潛在生物標志物,為抑郁癥臨床診斷及藥物作用機制研究提供依據。篩選符合納入標準的16例中重度抑郁癥患者和16例健康人分別作為疾病組和對照組,其中疾病組抑郁癥患者服用抗抑郁藥物帕羅西汀兩周。采集對照組、抑郁癥患者以及抑郁癥患者服用帕羅西汀兩周后的血清進行1H NMR測試,采用代謝組學技術結合多元統(tǒng)計方法分析血清中內源性代謝產物的變化及其規(guī)律,發(fā)現具有顯著性差異的代謝產物,結合相關代謝途徑及受試者工作曲線(ROC)分析發(fā)現潛在生物標志物,并進一步探討其與抑郁癥的相關性及應用于臨床診斷的可靠性和可行性。抑郁癥患者血清中谷氨酸、谷氨酰胺、丙氨酸、N-乙酰糖蛋白、亮氨酸及異亮氨酸的水平顯著升高,而葡萄糖水平顯著降低(P0.05,P0.01),而帕羅西汀對丙氨酸、N-乙酰糖蛋白、異亮氨酸及葡萄糖代謝水平具有顯著的回調作用(P0.05,P0.01),并調節(jié)谷氨酸、谷氨酰胺及異亮氨酸代謝水平使其具有向正常水平恢復的趨勢,因此可被確定為潛在生物標志物。上述生物標志物的應用將有助于提高抑郁癥臨床診斷的客觀性和抗抑郁藥物臨床療效評價的準確性。
[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.
【作者單位】： 山西大學中醫(yī)藥現代研究中心;山西大學化學化工學院;山西醫(yī)科大學第一醫(yī)院;
【基金】：國家自然科學基金資助項目(81173366;81441096)
【分類號】：R969

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