Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.
Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.
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DOI：
10.1371/journal.pone.0063624
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zou ZM
中科院分区：
文献类型：
--
作者：
Jia HM;Feng YF;Liu YT;Chang X;Chen L;Zhang HW;Ding G;Zou ZM
抑郁症是一种复杂的精神疾病，具有长期、反复发作的特点，其病因仍不清楚。在此，首次使用 1H NMR 和 UPLC-Q-TOF/MS 结合的综合方法对慢性不可预测轻度应激 (CUMS) 治疗的大鼠进行全面的尿液代谢组学研究。 CUMS 治疗后，超过 29 条代谢途径受到干扰，并且通过使用两种互补的分析技术鉴定了 36 种潜在的生物标志物。在已识别的生物标志物中，有 19 种（10、11、16、17、21-25 和 27-36）首次被报道为 CUMS 诱发抑郁症的潜在生物标志物。显然，本文提出了 CUMS 扰动的代谢途径的综合图谱，并扩展了之前在 CUMS 模型中报道的多种潜在生物标志物。四种代谢途径，包括缬氨酸、亮氨酸和异亮氨酸生物合成；苯丙氨酸、酪氨酸和色氨酸生物合成；色氨酸代谢；酮体的合成和降解在抑郁症的病理生理过程中影响最深。涉及上述四种代谢途径的15个潜在生物标志物（1-2、4-6、15、18、20-23、27、32、35-36）可能成为临床诊断的筛选标准并预测抑郁症的发展。此外，对 CUMS 治疗大鼠海马中芳香族 L-氨基酸脱羧酶 (DDC) 和吲哚胺 2, 3-双加氧酶 (IDO) 的蛋白质印迹分析结果表明，5-HT 和色氨酸的消耗、5-MT 的产生以及 DDC 和 IDO 表达的改变共同在抑郁症的发生和进展中发挥了关键作用。此外，NMR和LC-MS均未同时检测到任何潜在的生物标志物，这表明两种检测技术的互补性。因此，1H NMR和UPLC-Q-TOF/MS在代谢组学研究中的整合提供了一种识别与抑郁症相关的综合潜在生物标志物的方法，并有助于通过代谢途径的紊乱进一步了解抑郁症的潜在分子机制。
Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing 1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS) treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21–25, and 27–36) were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1–2, 4–6, 15, 18, 20–23, 27, 32, 35–36) involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC) and indoleamine 2, 3-dioxygenase (IDO) in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of 1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify the comprehensive potential depression-related biomarkers and helpful in further understanding the underlying molecular mechanisms of depression through the disturbance of metabolic pathways.
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作者：
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