Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
J Stroke Cerebrovasc Dis. 2020 Apr;29(4):104618. doi: 10.1016/j.jstrokecerebrovasdis.2019.104618. Epub 2020 Jan 20.
Metabolome profiling is used to identify biomarkers for acute ischemic stroke (AIS). Previous studies compared metabolite profiles in AIS and healthy controls, which did not account for factors that affect metabolome (genetics, medications). This pilot project evaluates the change in metabolite concentrations between the acute and chronic stage of stroke in the same cohort in order to minimize other factors impact.
We performed global metabolome profile on serum of 20 and urine of 12 stroke patients in acute (72 hours) and chronic (3-5.2 months) stage and compared relative peak values using Wilcoxon and orthogonal partial least squares discriminant analysis methods. Chronic stage metabolite concentrations were considered baseline. We performed analysis to identify significantly overrepresented pathways using MetaboAnalyst.
Three serum metabolites asparagine (P = .045), tyrosine (P = .015), and xylose (P = .003) had significantly higher concentrations in acute stage. Seven out of top 10 serum metabolites ranked by Wilcoxon test P value were related to amino acid (AA) metabolism. Two urine metabolites glycine (P = .03) and acetylcarnitine (P = .05) had significantly different concentrations in the acute stage. Five of the top 10 urine metabolites related to AA metabolism. We identified 6 significant pathways after false discovery rate correction that were upregulated in the acute stage: (1) Aminoacyl-tRNA synthesis, (2) nitrogen, (3) alanine, aspartate, and glutamate, (4) branched-chain AA, (5) arginine and proline, and (6) phenylalanine metabolism.
Longitudinal study design confirms that AA metabolism heavily involved in the pathophysiology of acute brain ischemia. Prospective longitudinal studies with a higher number of participants are needed to establish useful stroke biomarkers.
代谢组学分析被用于鉴定急性缺血性脑卒中（AIS）的生物标志物。既往研究比较了 AIS 患者和健康对照者的代谢谱，但未考虑影响代谢组学的因素（遗传、药物）。本研究项目旨在评估同一队列中 AIS 患者在急性期和慢性期之间代谢物浓度的变化，以最大限度减少其他因素的影响。
我们对 20 例急性（72 小时）和 12 例慢性（3-5.2 个月）期脑卒中患者的血清和尿液进行了代谢组学分析，采用 Wilcoxon 和正交偏最小二乘判别分析方法比较相对峰面积值。将慢性期的代谢物浓度作为基线。我们采用 MetaboAnalyst 分析方法鉴定显著上调的代谢通路。
血清中 3 种代谢物天冬酰胺（P=0.045）、酪氨酸（P=0.015）和木糖（P=0.003）在急性期浓度显著升高。Wilcoxon 检验 P 值排名前 10 的血清代谢物中有 7 种与氨基酸（AA）代谢有关。2 种尿液代谢物甘氨酸（P=0.03）和乙酰肉碱（P=0.05）在急性期浓度差异有统计学意义。前 10 种尿液代谢物中有 5 种与 AA 代谢有关。经假发现率校正后，有 6 条代谢通路显著上调，包括（1）氨酰-tRNA 合成、（2）氮、（3）丙氨酸、天冬氨酸和谷氨酸、（4）支链氨基酸、（5）精氨酸和脯氨酸、（6）苯丙氨酸代谢。
纵向研究设计证实 AA 代谢在急性脑缺血病理生理学中起着重要作用。需要开展纳入更多参与者的前瞻性纵向研究，以建立有用的脑卒中生物标志物。
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