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脑内出血性脑卒中脂肪酸生物标志物的代谢组学分析。

Metabolomic profiling of fatty acid biomarkers for intracerebral hemorrhage stroke.

机构信息

Analytical Center, Neurology Department of Affiliated Hospital, Institute of Neurology, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.

CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Talanta. 2021 Jan 15;222:121679. doi: 10.1016/j.talanta.2020.121679. Epub 2020 Sep 17.

Abstract

The identification of new biomarkers (e.g., metabolic biomarkers) will facilitate not only the diagnosis of stroke but also the differentiation of stroke subtypes, especially the discrimination of ischaemic stroke from intracerebral hemorrhage. Herein, we develop for the first time an ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS)-based targeted metabolomic method to screen the metabolic biomarkers of stroke and identify the fatty acid metabolite 20-hydroxy-leukotriene B4 (20-OH-LTB4) and its key enzyme cytochrome P450 family 4 subfamily F member 2 (CYP4F2) as the potential biomarkers for differentiating healthy persons, acute ischemic stroke (AIS) patients, and intracerebral hemorrhage stroke (ICH) patients. We evaluated 158 fatty acids and their metabolites in 177 serum samples obtained from 65 healthy volunteers, 70 AIS patients and 42 ICH patients, and identified the potential biomarkers associated with ICH by using multivariate statistical analysis. We found that 20-OH-LTB4 and arachidonic acid can be used to discriminate ICH patients from healthy individuals, and 20-OH-LTB4 and 17, 18-epoxy-eicosatetraenoic acid (7,18-EpETE) can be used to differentiate the subtypes of ICH and AIS. Especially, 20-OH-LTB4 may function as a potential biomarker for ICH diagnosis and risk assessment, and it can discriminate ICH patients from healthy individuals and AIS patients. Moreover, we identified CYP4F2 protein as a potential biomarker of ICH for prevention and treatment assessment. This method may provide a powerful platform for ICH diagnosis, prevention, and treatment assessment.

摘要

新生物标志物(例如代谢标志物)的鉴定不仅将有助于中风的诊断,还有助于中风亚型的区分,特别是有助于区分缺血性中风和脑出血。在此,我们首次开发了一种基于超高压液相色谱串联质谱(UHPLC-MS)的靶向代谢组学方法来筛选中风的代谢生物标志物,并确定了脂肪酸代谢产物 20-羟基白三烯 B4(20-OH-LTB4)及其关键酶细胞色素 P450 家族 4 亚家族 F 成员 2(CYP4F2)作为区分健康个体、急性缺血性中风(AIS)患者和脑出血中风(ICH)患者的潜在生物标志物。我们评估了 177 份血清样本中的 158 种脂肪酸及其代谢物,这些样本来自 65 名健康志愿者、70 名 AIS 患者和 42 名 ICH 患者,并通过多变量统计分析鉴定出与 ICH 相关的潜在生物标志物。我们发现,20-OH-LTB4 和花生四烯酸可用于区分 ICH 患者与健康个体,而 20-OH-LTB4 和 17,18-环氧二十碳四烯酸(7,18-EpETE)可用于区分 ICH 和 AIS 的亚型。特别是,20-OH-LTB4 可能作为 ICH 诊断和风险评估的潜在生物标志物,可将 ICH 患者与健康个体和 AIS 患者区分开来。此外,我们还鉴定出 CYP4F2 蛋白作为 ICH 的潜在生物标志物,用于预防和治疗评估。该方法可能为 ICH 的诊断、预防和治疗评估提供了一个强大的平台。

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