基于LC-MS技术对自然更年期（衰老）大鼠模型的代谢组学研究

摘要

Objective To further understand the natural metabolic characteristics of menopausal syndrome,and explore the role of biological pathways. Methods Our experiment adopted the HPLC-MS/MS technology of metabolomics researching methods, aiming at the comprehensive change characteristics in metabolism group level of menopausal rat and searching for age-related biomark⁃ers. The urine of 6 and 18 months rat was taken for HPLC-MS/MS metabolomics analysis. Besides,XCMS online analysis was used for positive and negative ion detection spectrum and the principal component analysis was used to identify biomarkers. Finally ,MetPA was used to implement a Google-map style interactive visualization system,which has analyzed the metabolic pathway. Pathway views were generated dynamically based on interactions with the visualized system. Results The TCA cycle,arginine and proline metabo⁃lism and aldehyde acid metabolism are related to aging rat metabolite pathways. Conclusion Age-related metabolic pathways are mainly related to the respiratory chain reaction and the urea cycle,which are influenced by liver mitochondrial function.%目的：为进一步了解自然更年期综合征的代谢特征，探索其过程中对已知或未知生物通路的作用，采用基于HPLC-MS/MS技术的代谢组学研究方法，通过分析老龄化大鼠代谢轮廓，旨在获得全面的更年期大鼠代谢组水平的变化特征，发现并筛选与年龄相关的生物标志物。方法首先对6月和18月龄大鼠尿液采用HPLC-MS/MS发现代谢组学分析方法，通过XCMS在线分析大鼠正负模式离子检测谱，对代谢谱HPLC-MS/MS分析实验中标记的代谢物进行鉴定，数据经主成分分析后筛选出差异性代谢物，最后以MetPA对HPLC-MS/MS实验中筛选出的代谢物组进行代谢通路分析。结果分析结果得到三羧酸循环、精氨酸和脯氨酸代谢和乙醛酸代谢3条与老龄化大鼠代谢相关的通路。结论由代谢网络图可见，与年龄相关的代谢通路主要和生物氧化呼吸链反应以及尿素循环有关，且这些代谢通路与肝脏线粒体功能相关性很大。