高等学校化学学报

高等学校化学学报 ›› 2011, Vol. 32 ›› Issue (1): 38.

• 研究论文 • 上一篇    下一篇

蟾酥急性毒性的代谢组学研究

梁晓萍1,2,张政1,4,胡坪3,钟宏福1,2,葛朝晖1,5,邹婷婷2,6,梁琼麟2,王义明2,罗国安1,2   

  1. 1. 华东理工大学药学院, 上海 200237;
    2. 清华大学化学系, 北京 100084;
    3. 华东理工大学化学与分子工程学院, 上海 200237;
    4. 江西中医学院药理学系, 南昌 330004;
    5. 沈阳药科大学药学院, 沈阳 110016;
    6. 北京工商大学化学与环境工程学院, 北京 100048
  • 收稿日期:2010-05-31 修回日期:2010-10-30 出版日期:2011-01-10 发布日期:2010-12-11
  • 通讯作者: 罗国安 E-mail:luoga@tsinghua.edu.cn
  • 基金资助:

    国家“新药创制”重大专项基金(批准号: 2008ZX09202, 2009ZX09311-001)和国家“十一五”科技支撑计划项目(批准号: 2006BAI08B04-01)资助.

Metabonomics Study on the Acute Toxicity of Toad Venom

LIANG Xiao-Ping1,2, ZHANG Zheng1,4, HU Ping3, ZHONG Hong-Fu1,2, GE Zhao-Hui1,5, ZOU Ting-Ting2,6, LIANG Qiong-Lin2, WANG Yi-Ming2, LUO Guo-An1,2*   

  1. 1. School of Phamacy, East China University of Science and Technology, Shanghai 200237, China;
    2. Department of Chemistry, Tsinghua University, Beijing 100084, China;
    3. College of Chemical and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China;
    4. Department of Pharmacology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;
    5. School of Phamacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
    6. College of Chemical & Environmental Engineering, Beijing Technology and Business University, Beijing 100048, China
  • Received:2010-05-31 Revised:2010-10-30 Online:2011-01-10 Published:2010-12-11
  • Contact: LUO Guo-An E-mail:luoga@tsinghua.edu.cn
  • Supported by:

    国家“新药创制”重大专项基金(批准号: 2008ZX09202, 2009ZX09311-001)和国家“十一五”科技支撑计划项目(批准号: 2006BAI08B04-01)资助.

PDF (PC)

被引次数

45

摘要： 本文中，我们运用代谢组学方法结合心电图分析对蟾酥导致的大鼠急性毒性进行了研究，通过超高效液相色谱-飞行时间质谱建立了大鼠血清的代谢指纹谱，采用主成分分析和正交偏最小二乘法判别分析法分析了对照组和各给药组之间的代谢物谱差异，通过变量重要性投影和T检验选取潜在的生物标志物，结合质谱同位素分析、数据库检索以及标准品对潜在生物标志物进行了鉴定。结果表明，蟾酥可导致心脏心率减慢、心律失常、甚至出现心肌梗塞现象，其导致心脏损伤的原因可能是通过阻碍自由脂肪酸再酰化或激活蛋白激酶通路干扰了脂质代谢，这对于阐述蟾酥毒性作用机理提供了新思路。

关键词: 蟾酥, 急毒性, 代谢组学, 超高效液相色谱/飞行时间质谱, 脂质代谢

Abstract: In this study, the metabonomics method coupled with electrocardiogram were applied to the study on the acute toxicity of toad venom. The profiles of serum samples were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/TOF-MS). The data were firstly processed with the software Markerlynx and then analyzed with the principal components analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA). The potential biomarkers were screened out according to the VIP (variable importance in projection) value and identified with i-fit, database and corresponding reference standards. The metabolites of significant intergroup differences were finally found to be lipids related to myocardial energy metabolism. According to the biological functions of the obtained potential biomarkers, it was deduced that the heart injury may be induced by disturbing lipid metabolism through hampering the re-acylation of free fatty acid or activating protein kinase pathway. This study provides a new approach to discover the underlying mechanism of toad venom toxicity.

Key words: Toad venom, Acute toxicity, Metabonomics, UPLC/TOF-MS, Lipid metabolism

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