基于1H NMR代谢组学方法分析马兜铃酸I诱导的雌雄小鼠急性肾毒性

高等学校化学学报 ›› 2010, Vol. 31 ›› Issue (5): 927.

基于¹H NMR代谢组学方法分析马兜铃酸I诱导的雌雄小鼠急性肾毒性

刘霞¹, 肖瑛¹, 高红昌², 任进¹, 林东海¹

1. 中国科学院上海药物研究所分析化学研究室, 新药研究国家重点实验室, 安全性评价中心, 上海 201203;
2. 温州医学院药学院, 分析测试中心, 温州 325035

收稿日期:2009-05-14 出版日期:2010-05-10 发布日期:2010-05-10
通讯作者: 林东海. E-mail: dhlin@mail.shcnc.ac.cn; 任进. E-mail: jren@mail.shcnc.ac.cn; 高红昌. E-mail: gaohc27@gmail.com
基金资助:
国家自然科学基金(批准号: 20705037)、温州医学院科研启动经费(批准号: QTJ08008)、中国科学院知识创新工程青年人才领域前沿和重要方向项目(批准号: SIMM0709QN-07, KSCX2-YW-R-118)资助.

Metabonomic Study of Aristolochic Acid I-induced Acute Renal Toxicity Urine at Female and Male C57BL/6J Mice Based on ¹H NMR

LIU Xia¹, XIAO Ying¹, GAO Hong-Chang^2*, REN Jin^1*, LIN Dong-Hai^1*

1. Analytical Chemistry Laboratory, State Key laboratory of New Drug Research, Centre for Drug Safety and Evaluation Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
2. Analysis and Testing Center, Pharmacy School, Wenzhou Medical College, Wenzhou 325035, China

Received:2009-05-14 Online:2010-05-10 Published:2010-05-10
Contact: LIN Dong-Hai. E-mail: dhlin@mail.shcnc.ac.cn; REN Jin. E-mail: jren@mail.shcnc.ac.cn; GAO Hong-Chang. E-mail: gaohc27@gmail.com
Supported by:
国家自然科学基金(批准号: 20705037)、温州医学院科研启动经费(批准号: QTJ08008)、中国科学院知识创新工程青年人才领域前沿和重要方向项目(批准号: SIMM0709QN-07, KSCX2-YW-R-118)资助.

摘要/Abstract

摘要：

基于¹H NMR的代谢组学方法, 分析了C57BL/6J小鼠尿样的代谢特征, 揭示出马兜铃酸I(AAI)导致急性肾毒性的分子机理及其在雌性和雄性小鼠上差异的根源. 研究结果表明, AAI的急性肾毒性主要来自AAI给药后抑制了体内的三羧酸(TCA)循环和能量代谢, 破坏了体内肠道菌群的生态平衡, 改变了肾脏细胞内外的渗透压, 从而引起了肾小管的损伤. 代谢模式分析显示雄性小鼠对AAI的肾毒性比雌性小鼠更敏感, 可能源于雄性小鼠本身更低的能量代谢. 结果表明, 基于尿样¹H NMR代谢组学方法有可能为药物的毒性机制和毒性性别差异研究提供新思路.

关键词: 马兜铃酸; 肾毒性; 代谢组学; 核磁共振; 毒性性别差异

Abstract:

The present work illustrates the metabolic changes of aristolochic acid I-induced acute renal toxicity urine at male and female C57BL/6J mice, which would help to understand the mechanism of renal toxicity and the differences in the metabolism at female and male mice after AAI treatment. The results showed that AAI nephrotoxicity mainly resulted from AAI inhibited the tricaboxylic acid cycle and energy metabolism,damaged the ecology of intestinal flora, changed the osmotic pressure inside and outside the kidney cells, depressed creatinine clearance rate and caused the injury of renal tubular and glomerular. Metabolic pattern analysis also showed that male mice were more sensitive to AAI renal toxicity than the female. These results suggested that urine ¹H NMR-based metabonomics probably provides a novel insight into the study of drug toxicity mechanism and the toxicity gender differences.

Key words: Aristolochic acid; Renal toxicity; Metabonomics; NMR; Toxicity gender difference

TrendMD:

刘霞, 肖瑛, 高红昌, 任进, 林东海. 基于¹H NMR代谢组学方法分析马兜铃酸I诱导的雌雄小鼠急性肾毒性. 高等学校化学学报, 2010, 31(5): 927.

LIU Xia, XIAO Ying, GAO Hong-Chang*, REN Jin*, LIN Dong-Hai*. Metabonomic Study of Aristolochic Acid I-induced Acute Renal Toxicity Urine at Female and Male C57BL/6J Mice Based on ¹H NMR. Chem. J. Chinese Universities, 2010, 31(5): 927.

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基于¹H NMR代谢组学方法分析马兜铃酸I诱导的雌雄小鼠急性肾毒性

Metabonomic Study of Aristolochic Acid I-induced Acute Renal Toxicity Urine at Female and Male C57BL/6J Mice Based on ¹H NMR

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