分析化学2017，Vol.45Issue(4)：565-573,9.DOI:10.11895/j.issn.0253-3820.160800
黄芪口服液降低大鼠顺铂毒性作用机制的尿液代谢组学研究
Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats
摘要
Abstract
A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.关键词
黄芪口服液/顺铂/尿液/代谢组学/液相色谱-飞行时间质谱联用/毒性Key words
Huangqi oral solution/Cisplatin/Urine/Metabolomics/Liquid chromatography-time-of-flight mass spectrometry/Toxicity引用本文复制引用
宋慧婷,李长印,万瑶瑶,丁选胜,戴国梁,刘史佳,居文政..黄芪口服液降低大鼠顺铂毒性作用机制的尿液代谢组学研究[J].分析化学,2017,45(4):565-573,9.基金项目
本文系国家自然科学基金项目(No.81503300),江苏省自然科学基金项目(No.BK20131035),江苏省中医院高峰人才项目(No.y2014rc17)资助 （No.81503300）
This work was supported by the National Natural Science Foundation of China (No.81503300). （No.81503300）
