基于代谢组学技术对雷公藤多苷和奥硝唑诱导大鼠弱精子症的病理机制研究

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (7): 721-730.

• 基础研究 • 下一篇

基于代谢组学技术对雷公藤多苷和奥硝唑诱导大鼠弱精子症的病理机制研究

顾惠琴¹，赵昂²，周艳芬²，李静²，范丽²，王聪²，郭素菡²，王宇²，张琪²，马博²

¹靖江市人民医院，靖江 214500，江苏； ²药动药效研究与评价中心，南京工业大学药学院，南京 210009，江苏

收稿日期:2016-12-05 修回日期:2017-02-08 出版日期:2017-07-26 发布日期:2017-07-19
通讯作者: 马博，男，博士，副教授，研究方向：代谢组学，药物代谢动力学。 Tel:025-83172105 E-mail:mabo201012@njtech.edu.cn
作者简介:顾惠琴，女，本科，主管药师，研究方向：药物代谢动力学、代谢组学。 Tel:13615198198 E-mail:1679551377@qq.com 赵昂，共同第一作者，男，硕士研究生，研究方向：药物代谢动力学、代谢组学。 Tel:15051806018 E-mail:eric494@qq.com
基金资助:
国家自然科学基金项目（81373478）

Metabolomic study on the mechanism of asthenospermia induced by tripterygium glycosides and ornidazole in rats via GC-MS approach

GU Huiqing ¹, ZHAO Ang ², ZHOU Yanfen², LI Jing ², FAN Li ², WANG Cong ², GUO Suhan², WANG Yu ², ZHANG Qi², MA Bo²

¹Jingjiang Municipal People's Hospital, Jingjiang 214500, Jiangsu, China; ²School of Pharmaceutical Sciences, Nanjing Technology University, Nanjing 210009, Jiangsu, China

Received:2016-12-05 Revised:2017-02-08 Online:2017-07-26 Published:2017-07-19

摘要/Abstract

摘要：

目的: 通过基于气相色谱串联质谱（GC-MS）的代谢组学技术研究和比较雷公藤多苷与奥硝唑分别导致大鼠弱精子症的潜在生物标记物和可能的病理机制。方法: 使用雷公藤多苷和奥硝唑分别干预诱导大鼠弱精症疾病动物模型。每两周采集血清和附睾液样本。采用GC-MS代谢组学技术全面测定大鼠血清及附睾液中的内源性小分子代谢产物。并通过偏最小二乘判别法（PLS-DA）对正常组、雷公藤多苷和奥硝唑造模病理组血清和附睾液中的内源性小分子代谢产物进行多元数据分析，寻找两药病理模型中的差异代谢物，确定潜在生物标记物，探索和比较两种药物可能的毒性机制。结果: 采用有监督模式下的PLS-DA通过分析GC-MS所得的代谢物图谱可以将雷公藤多苷和奥硝唑的病理组同正常组的显著地区分，并且两药模型组的代谢图谱也能得到较好的分离。与正常组相比，雷公藤模型组血清中赖氨酸、苏氨酸等氨基酸显著增加，附睾液中琥珀酸上调，尿素、胆固醇、肌醇等下调；奥硝唑模型组血清中多种氨基酸含量均有所降低，附睾液中二羟丙酮磷酸、核酮糖-5-磷酸出现显著性上升。结论: 通过基于GC-MS代谢组学技术可以高效地识别雷公藤多苷和奥硝唑诱导的大鼠动物模型的病理进程变化，相比较常规性腺指标的观察和检测更为快速、灵敏。代谢组检测中筛选所获得的差异代谢物提示着雷公藤多苷和奥硝唑诱发大鼠弱精症涉及不同的代谢途径，因此病理机制存在着显著差异。

关键词: 代谢组学, 弱精子症, 雷公藤多苷, 奥硝唑, 气相色谱-质谱

Abstract:

AIM: To explore the protential biomarkers and the mechanism of asthenospermia induced by tripterygium glycosides (TG) and ornidazole (ONZ), respectively, relying on gas chromatography-mass spectrometry (GC-MS)-based metabolomics. METHODS: Wistar rats were orally administrated with TG(40 mg·kg-1·d-1) and ONZ (400 mg·kg-1·d-1) for 30 days, respectively. Serum and epididymal fluid samples were collected every two weeks. A metabolomic approach based on GC-MS was employed to identify endogenous metabolites in serum and epididymal fluid samples, respectively. Data acquired were further evaluated by multivariate statistical analysis and a partial least squares discriminant analysis (PLS-DA) was applied to finding potential biomarkers.RESULTS:PLS-DA clearly profiled a time-dependent alternation of metabolic phenotype of serum and epididymal fluid samples. The clear classifications between the normal and TG group, the normal and ONZ group as well as TG group and ONZ group were achieved. And some significant metabolites were successfully filtered. The levels of lysine, threonine and some other amino acids in serum were higher in the TG-treated rats than those in the normal rats. In the ONZ-treated rats, concentrations of amino acids in serum were declined. In addition, the level of butanedioic acid was increased in epididymal fluid of TG-treated rats, while the levels of urea, cholesterol, inositol, etc were varied in an opposite manner. Significant changes were observed in the levels of dihydroxyacetone phosphate and ribulose-5-phosphate in epididymal fluid of ONZ-treated rats, compared with the normal rats. CONCLUSION: The metabolomics technology as a high-efficiency tool can be used to distinguish the difference between TG-induced and ONZ-induced asthenospermia in rats. More importantly, TG-induced and ONZ-induced asthenospermia may have different etiology due to disturbing different endogenous metabolic pathways.

Key words: metabonomics, asthenospermia, tripterygium glycosides, ornidazole, GC-MS

中图分类号:

R965.2

顾惠琴，赵昂，周艳芬，李静，范丽，王聪，郭素菡，王宇，张琪,马博. 基于代谢组学技术对雷公藤多苷和奥硝唑诱导大鼠弱精子症的病理机制研究[J]. 中国临床药理学与治疗学, 2017, 22(7): 721-730.

GU Huiqing, ZHAO Ang, ZHOU Yanfen, LI Jing, FAN Li, WANG Cong, GUO Suhan, WANG Yu, ZHANG Qi, MA Bo. Metabolomic study on the mechanism of asthenospermia induced by tripterygium glycosides and ornidazole in rats via GC-MS approach[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(7): 721-730.

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基于代谢组学技术对雷公藤多苷和奥硝唑诱导大鼠弱精子症的病理机制研究

Metabolomic study on the mechanism of asthenospermia induced by tripterygium glycosides and ornidazole in rats via GC-MS approach

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