基于气相色谱-飞行时间质谱技术的佐剂性关节炎大鼠尿液代谢组学的研究

摘要

Adjuvant arthritis( AA)rats induced by Freund’s complete adjuvant( FCA)were used to observe the changes of the degree of swelling in the toes and pathomorphology of ankle joint tissue. Gas chromatography-time-of-flight mass spectrometry ( GC-TOF MS ) was employed to detect the metabolite spectrum in rat urine with AA,and the data were analyzed by principal component analysis( PCA),partial least squares-discriminant analysis( PLS-DA) and orthogonal partial least squares-discriminant analysis( OPLS-DA),and to explore its possi-ble pathogenesis. Several metabolites based on the variable importance in the projection values ( VIP﹥1),P value(﹤0. 05)and screening in databases were identified. The results showed that 20 potential biomarkers such as isocitric acid,α-ketoglutaric acid,citraconic acid,creatine and 3-hydroxybutyric acid which had a significant contribution to classification were selected. Com-paring with the normal group,AA rats present an abnormal metabolism. This study illustrates that AA metabolomics pathogenesis may be related to regulating the dysfunction of energy metab-olism,amino acid metabolism and fatty acid metabolism.%采用弗氏完全佐剂（ FCA）诱导佐剂性关节炎（ AA）大鼠模型，观察大鼠足趾肿胀度和踝关节组织的病理学形态变化。应用气相色谱-飞行时间质谱（ GC-TOF MS）技术检测 AA 大鼠尿液代谢物谱，并对数据进行主成分分析（ PCA）、偏最小二乘法-判别分析（ PLS-DA）及正交偏最小二乘法-判别分析（ OPLS-DA），探讨可能的发病机制。通过变量重要性投影值（ VIP ﹥1）和 P值（﹤0.05），筛选出尿液中的差异代谢物。在模型组大鼠的尿液中共发现异柠檬酸、α-酮戊二酸、柠康酸、肌酸、3-羟基丁酸等20种差异代谢物。推断 AA代谢组学的发病机制可能与能量代谢、氨基酸代谢、脂肪酸代谢途径有关。