基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究  

Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

作　　者：王学雷 晁玉凡 高松燕 董昕 温晓飞 WANG Xuelei;CHAO Yufan;GAO Songyan;DONG Xin;WEN Xiaofei(Department of Urology,Shanghai East Hospital,Shanghai 200120,China;School of Pharmacy,Naval Medical Universiry,Shanghai 200433,China)

机构地区：[1]上海东方医院泌尿外科,上海200120 [2]海军军医大学药学院测试中心,上海200433

出　　处：《药学实践杂志》2019年第2期126-134,共9页Journal of Pharmaceutical Practice

基　　金：上海市浦东新区科技发展基金(PKJ2013-Y21);上海市科学技术委员会科研计划项目(15401900800)

摘　　要：目的通过研究草酸钙结石小鼠尿液中代谢物的变化,探究草酸钙结晶导致肾损伤的内在机制。方法以乙醛酸盐诱导的小鼠草酸钙结晶模型为对象,采用基于超高效液相-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)的代谢组学方法测定尿液中内源性代谢物的变化,并采用SIMCA-P进行多元统计分析,Metabo Analyst软件进行代谢物通路分析。结果与正常组相比,模型组小鼠的肾组织出现明显的钙盐沉积且血清中的肌酐和尿素氮含量异常升高,肾脏出现损伤;从尿液中筛选出尿酸、牛磺酸、苯丙氨酸等21个差异代谢物。结论通过代谢物通路分析,差异代谢物主要涉及氨基酸代谢、能量代谢、牛磺酸代谢、嘌呤代谢和VB_6代谢,为进行结石疾病机制研究以及早期标志物的筛选提供了重要参考。Objective To explore the intrinsic mechanism of kidney injury due to calcium oxalate crystal by the study on the changes of metabolites in the urine of mice.Method UPLC-Q-TOF/MS-based metabolomics method was used to determine the changes of endogenous metabolites in mice urine with glyoxylate-induced mouse calcium oxalate crystal model.The multivariate statistics analysis and metabolite pathway analysis were performed by SIMCA-P and Metabo Analyst software respectively.Result Compared with the control group,the kidney tissue of the model group showed obvious calcium salt deposition and the serum creatinine and urea nitrogen levels increased abnormally.21 differential metabolites,such as uric acid,taurine and phenylalanine,were detected from the urine.Conclusion The differential metabolites mainly involve amino acid metabolism,energy metabolism,taurine metabolism,purine metabolism and VB 6 metabolism,which is of great importantce to the mechanism study and the biomaker screening for the early stage stone disease.

关 键 词：代谢组学 草酸钙结石 超高效液相-串联质谱 乙醛酸盐 差异代谢物 

分 类 号：R917[医药卫生—药物分析学]