基于UPLC-MS/MS^E方法研究马兜铃酸肾病大鼠的血清代谢组学  

Serum metabolomic study of aristolochic acid nephropathy in rats based on UPLC- MS/MS^E

作　　者：张莉[1] 孟梅霞[1] 安军民[1] 王昌[1] 畅飞[1] 赵英永[2] 

机构地区：[1]西安市第四医院,西安710004 [2]西北大学生命科学学院,西安710069

出　　处：《药物分析杂志》2014年第11期1948-1953,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：教育部"新世纪优秀人才计划"项目(NCET-13-0954);国家自然科学基金(81001622);陕西省国际合作项目(2013KW3I-01)

摘　　要：目的:基于超高效液相色谱-四极杆时间飞行高清质谱串联(UPLC-QTOF/HDMS)-代谢组学方法研究马兜铃酸Ⅰ诱导的马兜铃酸肾病(AAN)的代谢指纹图谱。方法:基于UPLC-QTOF/HDMS的代谢组学方法测定AAN大鼠血清,质谱数据采用Marker Lynx软件处理,然后使用主成分分析和正交校正的偏最小二乘判别分析法分析AAN模型组和正常对照组之间的代谢物谱差异,并通过S-plot图选取潜在的生物标示物,通过精确分子量、同位素分布、MSE信息和对照品对照,再通过检索HMDB等数据库对潜在的生物标示物进行鉴定。结果:用代谢组学方法鉴定了10个生物标示物,马兜铃酸Ⅰ上调了鹅去氧胆酸、胆酸、牛磺鹅脱氧胆酸、硫酸对甲酚、肌酐、7-酮基脱氧胆酸、硫酸吲哚酚和12-酮基脱氧胆酸,同时下调了溶血卵磷脂(15∶0)和溶血卵磷脂(17∶0)。结论:马兜铃酸诱导的肾损伤干扰了磷脂、胆汁酸、氨基酸的代谢。基于UPLC-QTOF/HDMS代谢组学法能够应用于马兜铃酸诱导的AAN的研究。Objective： To employ ultra performance liquid chromatography coupled with quadrupole time- of-flight high- denition mass spectrometry（ UPLC- QTOF / HDMS） for the study of serum metabolic profiling of aristolochic acid- induced aristolochic acid nephropathy（ AAN） in rats. Methods： Serum from AAN rats and control rats were determined by UPLC- QTOF / HDMS- based metabolomics approach. The difference of the metabolic profile of the AAN and normal control groups were analyzed by principal component analysis and discriminated by orthogonally corrected partial least squares. Potential biomarkers were screened by using S- plot and were identified by comparison with the accurate mass,isotopic pattern and MS^Efragments information as well as retrieval of data bases such as HMDB. Results： Ten metabolites were identified as potential biomarkers. The upregulation of chenodeoxycholic acid,cholic acid,taurochenodesoxycholic acid,creatinine,7- ketodeoxycholic acid,12- ketodeoxycholic acid,indoxyl sulfate and p- cresol sulfate and the downregulation of Lyso PC（ 15 ∶ 0） and Lyso PC（ 17 ∶ 0） by aristolochic acid I were observed. Conclusion： The perturbations of bile acid metabolism,amino acid metabolism and phospholipid metabolism due to kidney damage induced by aristolochic acid were observed in AAN rats. The study showed that the UPLC- MS / MS^E- metabonomics could be applied to investigation of aristolochic acid- induced AAN.

关 键 词：马兜铃酸肾病(AAN) 马兜铃酸肾毒性 代谢组学 生物标示物鉴定 鹅去氧胆酸 胆酸 牛磺鹅脱氧胆酸 硫酸对甲酚 肌酐 酮基脱氧胆酸 硫酸吲哚酚 溶血卵磷脂 磷脂 胆汁酸 氨基酸 代谢指纹图谱 

分 类 号：R917[医药卫生—药物分析学]