哌甲酯干预儿童多动症患者尿液的代谢组学研究

Study on Metabolomic Urine in Children with ADHD Treated with Methylphenidate

目的基于代谢组学方法研究哌甲酯干预儿童多动症患者尿液内源性代谢物的变化,并探索哌甲酯的作用机制。方法采用气相色谱-质谱联用技术(GC-MS)检测37例儿童多动症患者哌甲酯干预前(病例0周组)、干预6周(病例6周组)、干预12周(病例12周组)和同期40例健康者(对照组)尿液内源性代谢物,经正交偏最小二乘法(OPLS)分析,寻找显著差异的变量,鉴定潜在生物标志物。结果对照组、病例0周组、病例12周组的尿液代谢谱发生了明显变化,病例0周组与对照组的代谢谱能够区分,同时病例12周组样本远离病例0周组,靠近对照组;利用商业化的代谢物谱库(如Wiley和NIST质谱库)及本实验室建立的标准品代谢物谱库鉴定了24种相关代谢标志物,哌甲酯干预后,这些代谢物的水平逆转到正常水平。结论本研究表明哌甲酯治疗儿童多动症具有良好的疗效,其作用机制可能与丙酮酸代谢、色氨酸代谢、苯丙氨酸代谢、甘氨酸,丝氨酸和苏氨酸代谢等代谢异常有关,代谢组学从机体整体代谢角度揭示了哌甲酯治疗儿童多动症的作用机制。

Objective To study the effect of methylphenidate on urinary endogenous metabolites in children with ADHD, and to ex- plore the mechanism of methylphenidate. Methods The metabolites of urine in 37 children with ADHD treated with methylphenidate be- tore intervention （ case 0 week group） , intervention for 6 weeks （6 weeks group） , intervention 12 weeks （ 12 weeks group, and 4-0 health- y subjects （control group） were measured by gas chromatography - mass spectrometry （ GC - MS） , and analyzed by orthogonal partial least squares （OPLS） to find the significant differences biomarkers. Results The urine metabolic profile of the control group, the 0 week group and the 12 week group showed obvious changes. The metabolic profile of the 0 week group and the control group was differenti- ated, and the 12 week group was away from the 0 week group, and closed to the control group. 24 significant differences metabolites were identified using commercially available metabolite libraries （such as the Wiley and NIST mass pools） and the standard metabolite library established in our laboratory. The levels of these metabolites were reversed to normal level due to methylphenidate intervention. Conclusion This study shows that methylphenidate has a good curative effect on children with ADHD. Its mechanism is related to the metabolic abnormalities of pyruvate metabolism, tryptophan metabolism, phenylalanine metabolism, glycine, serine and threonine metabo- lism. The possible mechanism of methylphenidate in the treatment of children with ADHD was revealed from the overall metabolic point of the body. Metabolomics reveals possible therapeutic mechanism of methylphenidate for children with ADHD from overall metabolism of the body.