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

引用本文: 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. doi: 10.11895/j.issn.0253-3820.160800 shu

Citation: SONG Hui-Ting, LI Chang-Yin, WAN Yao-Yao, DING Xuan-Sheng, DAI Guo-Liang, LIU Shi-Jia, JU Wen-Zheng. Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats[J]. Chinese Journal of Analytical Chemistry, 2017, 45(4): 565-573. doi: 10.11895/j.issn.0253-3820.160800 shu

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

1.
南京中医药大学附属医院临床药理实验室, 南京 210029;
2.
中国药科大学药学院, 南京 211198
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

摘要: 采用基于液相色谱-飞行时间质谱联用（LC-TOF-MS）技术的代谢组学方法，分析大鼠尿液内源性代谢物的变化，研究黄芪口服液（HO）降低大鼠顺铂（CDDP）毒性的作用机制。采用低剂量多次腹腔注射CDDP的方法建立CDDP染毒大鼠模型，并连续给予16天HO。于第18天收集正常对照（Control）组、顺铂模型（CDDP）组和黄芪口服液（HO）组大鼠的24 h尿液，进行LC-TOF-MS分析，以获取尿液代谢物组数据集，对所得数据进行主成分分析（PCA）和正交偏最小二乘法-判别分析（OPLS-DA）等多元统计分析，以筛选潜在生物标志物。于第20天采集大鼠血清测定肌酐和尿素氮水平。血清指标测定结果表明，HO可以显著降低CDDP染毒大鼠的肌酐和尿素氮水平（p< 0.05）。PCA得分图显示，3组可分别聚类，HO组位于Control组和CDDP组中间，表明HO可部分改善CDDP所致大鼠尿液代谢产物的异常变化。综合OPLS-DA分析、t检验和倍数变化分析结果，最终共筛选并初步鉴定出35个尿液代谢产物作为HO减毒相关的潜在生物标记物。代谢通路分析结果表明，HO可通过纠正体内氨基酸代谢、能量代谢和核苷酸代谢等通路的紊乱，降低CDDP所致机体毒性。

关键词:

English

Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats

1.
Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China;
2.
School of pharmacy, China Pharmaceutical University, Nanjing 211198, China
Received Date: 01 November 2016
Revised Date: 30 December 2016
Fund Project:
This work was supported by the National Natural Science Foundation of China (No. 81503300).

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.

Key words:

Huangqi oral solution
/ Cisplatin
/ Urine
/ Metabolomics
/ Liquid chromatography-time-of-flight mass spectrometry
/ Toxicity

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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

English

Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats

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中国化学会秘书处

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

English

Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats

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