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弗氏完全佐剂诱导大鼠痛觉过敏的尿液代谢组学研究

Urinary metabolomics of complete Freund's adjuvant-induced hyperalgesia in rats.

作者信息

Liu Yang, Chen Hui, Lu Jun, Jiang Youshui, Yang Rui, Gao Songyan, Dong Xin, Chen Wei

机构信息

Student Brigade, Second Military Medical University, Shanghai, 200433, China.

Department of Anesthesiology, Changhai Hospital, Shanghai, 200433, China.

出版信息

Biomed Chromatogr. 2017 Jun;31(6). doi: 10.1002/bmc.3886. Epub 2017 Jan 5.

DOI:10.1002/bmc.3886
PMID:28058725
Abstract

The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty-four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.

摘要

本研究的目的是证明痛觉过敏模型中代谢组学变化的差异,并找到痛觉过敏的有效生物标志物。将7只大鼠置于代谢笼中。使用含有500μg完全弗氏佐剂(CFA)的乳剂诱导痛觉过敏。在注射CFA之前以及注射后第1、3和7天收集尿液样本。超高效液相色谱与四极杆飞行时间质谱联用(UHPLC-Q-TOF/MS)用于对CFA诱导的痛觉过敏模型中的尿液代谢变化进行定量分析。使用偏最小二乘判别分析来分析四组大鼠代谢谱之间的差异。鉴定出34种潜在的尿液代谢物生物标志物,其变化趋势与疼痛阈值相似。这些潜在的生物标志物涉及11条代谢途径,如下:丙氨酸、天冬氨酸和谷氨酸代谢;抗坏血酸和醛糖代谢;甘油酯代谢;甘油磷脂代谢;组氨酸代谢;苯丙氨酸代谢;鞘脂代谢;色氨酸代谢;酪氨酸代谢;缬氨酸、亮氨酸和异亮氨酸生物合成;以及维生素B6代谢。这些结果可能会增进我们对痛觉过敏的理解,并为痛觉过敏的临床诊断提供依据。

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