慢性疲劳综合征中学生运动前后尿液差异代谢物的比较

Comparison of differential metabolites in urine of the middle school students with chronic fatigue syndrome before and after exercise

目的:探讨慢性疲劳综合征(CFS)中学生运动前后尿液的差异代谢物及其代谢通路特征,阐述慢性疲劳综合征的代谢机制。方法:依据美国疾病预防控制中心关于CFS的筛选标准,选取8名17～19岁男性CFS中学生作为受试对象,同时选择来自同一学校的8名同龄、同性别健康中学生作为对照组。受试者进行一次改良的哈佛台阶运动(上下台阶30次/min,持续3 min),采集运动前后的尿液,以液相-质谱联用(LC-MS)法检测其差异代谢物;采用多维统计法对所检测到的代谢物进行主成分分析(PAC)和正交偏最小二乘判别分析(OPLS-DA);通过MetPA数据库分析与差异代谢物相关的代谢通路。结果:与对照组相比较,运动前CFS组筛选出肌酸、吲哚乙醛、植物鞘氨醇和焦谷氨酸4个差异代谢物,其含量均显著下降(P<0.05或P<0.01);运动后CFS组检测出11个差异代谢物,依次是壬二酸、甲基腺苷、乙酰肉碱、癸酸、皮质酮、肌酸、左炔诺孕酮、泛酸、焦谷氨酸、黄嘌呤核苷和黄尿酸,其中除甲基腺苷和肌酸比对照组显著升高(P<0.05)外,其他9个差异代谢物均较对照组显著降低(P<0.05或P<0.01)。将上述15个差异代谢物分别输入MetPA数据库进行代谢通路权重得分分析,结果显示,运动前CFS组只检测出精氨酸-脯氨酸代谢通路紊乱,标记代谢物为肌酸;而运动后检测出精氨酸-脯氨酸代谢、泛酸与辅酶A生物合成、类固醇激素生物合成3条代谢通路存在障碍,标记代谢物依次是:肌酸、泛酸和皮质酮。结论:运动干预前,CFS中学生的精氨酸-脯氨酸代谢通路紊乱被检出;施加运动后,又检测出其类固醇激素生物合成代谢通路与泛酸和辅酶A代谢通路也存在代谢紊乱情况。

Objective： To study the differential metabolites in urine and the characteristics of metabolic pathway of middle school students with chronic fatigue syndrome（ CFS） before and after exercise,and then explain the metabolic mechanism of CFS. Methods：Eight male middle school students（ age： 17-19） with CFS were selectedas the CFS group according to CFS screening criteria of the U.S. centers.At the same time,8 male health students of the same age from the same school were selected as the control group. They were administrated to do one-time exercise on the improved Harvard step（ up and down steps 30 times/min for 3 minutes）. Their urinewascollected before and after exercise,and the differential metabolitesin urine were detected by liquid chromatography-mass spectrometry（ LCMS）. The multidimensional statistical methods were used to analyze the metabolites by principal component analysis（ PCA） and orthogonal projections to latent structures-discriminant analysis（ OPLS-DA）. Finally,MetPA database was used to analyze the metabolites and to construct the correlativemetabolic pathways. Results： Compared with the control group,the creatine,indoleacetaldehyde,phytosphingosine and pyroglutamic acid were selected as differential metabolites and the contents of those were decreased significantly（ P〈0.05 or P〈0.01） in CFS groupbefore the step movement. However,11 differential metabolitesin CFS group were selected out after exercise,which were nonanedioic acid,methyladenosine,acetylcarnitine,capric acid,corticosterone,creatine,levonorgestrel,pantothenic acid,pyroglutamic acid,xanthosine and xanthurenic acid in sequence,the contents of methyladenosine and creatinewere significantly increased（ P〈0.05） and the contents of the other 9 differentialmetabolites were significantly decreased（ P 0.05 or P 0.01）compared with the control group. The 15 differential metabolites mentioned above were input MetPA database in order to analyze the metabolic pathways weighted score. The results showed that the arginine-proline metabolism pathway disordersweredetected in the CFS group before exercise,the marker metabolite wascreatine. And 3 metabolic pathwaysdisorder weredetectedin the CFS groupafter exercise,which were arginine-proline metabolism,biosynthesis of pantothenic acid and Co A,steroid hormone biosynthesis,and the marker metabolites,in turn,werecreatine,pantothenic acid and corticosterone. Conclusion： The disorder of arginine-proline metabolic pathway is detected in CFS middle school students before exercise intervention. After exercise,it can be detected that the steroid hormone biosynthetic metabolic pathway,pantothenic acid and Co A metabolic pathways also have metabolic disorders.