基于代谢组学的抽动障碍患儿尿液生物标志物研究

Study on urine biomarkers in children with tic disorder based on metabonomics

目的筛选抽动障碍患儿尿液相关生物标志物,探析抽动障碍的生物学实质。方法采用液-质联用技术(LC-MS)、气-质联用技术(GC-MS)和化学计量学分析研究技术,对2019年10月—2020年3月在北京中医药大学东方医院儿科就诊的抽动障碍患儿(抽动障碍组)及健康体检儿童(正常组)尿液进行检测,筛选出抽动障碍患儿尿液代谢生物标记物,分析其代谢通路及生物学意义。结果共纳入抽动障碍患儿及健康体检儿各30例,2组年龄、性别比较差异均无统计学意义(P均>0.05)。经尿液代谢组学检测分析,筛选出与抽动障碍相关的生物标记物50余种,包括正离子模式下的对羟基苯乙酸、1-甲基组氨酸、4-吡啶氧酸、吲哚乙酸等;负离子模式下的N6-乙酰-L-赖氨酸、硫酸吲哚酯、胸腺嘧啶等;差异性标记物主要涉及氨基酸代谢、不饱和脂肪酸的生物合成、类固醇激素代谢等代谢通路。结论所筛选的生物标记物及其代谢通路在自身免疫功能以及炎症的启动、发展、消退等方面具有重要的调节作用,考虑可能是抽动障碍患儿免疫功能改变、炎症因子增加的上游原因,不仅可作为抽动障碍患儿独特的代谢图谱,而且为抽动障碍的发病机制及进一步研究靶点提供了依据。

Objective It is to screen the urine biomarkers of children with tic disorder(TD)and to explore the biological essence of TD.Methods The urine of children with TD(TD group)and healthy children after physical examination(normal group)treated at the Pediatrics Department of Dongfang Hospital,Beijing University of Chinese Medicine from October 2019 to March 2020 were detected by liquid chromatograohy-mass spectrometry(LC-MS),gas chromatograohy-mass spectrometry(GC-MS)and chemometric analysis and research technology.The urine metabolism biomarkers of children with TD were screened,and their metabolic pathways and biological significance were analyzed.Results 30 TD children and 30 healthy children were enrolled,and there was no significant difference in age and gender between the two groups.More than 50 biomarkers related to TD were screened out after urine metabonomics detection and analysis,including p-Hydroxyphenylacetic acid,1-methylhistidine,4-pyridoxic acid,indoleacrylic acid in positive ion mode,N6-acetyl-L-lysine,indoxyl sulfate,thymidine in negtive ion mode.These different biomarkers mainly involved in the metabolic pathways such as amino acid metabolism,unsaturated fatty acid biosynthesis,steroid hormone metabolism and so on.Conclusion The selected biomarkers and their metabolic pathways play an important role in the regulation of autoimmune function and the initiation,development and regression of inflammation,which may be the upstream cause of changes in immune function and increase of inflammatory factors in children with TD.It can not only be used as a unique metabolic map of children with TD,but also provide a basis for the pathogenesis of TD and further research targets.