JAK/STAT通路抑制剂对C57BL/6小鼠血清代谢组影响的1H NMR研究

doi:10.11938/cjmr20182630

波谱学杂志 ›› 2018, Vol. 35 ›› Issue (2): 198-203.doi: 10.11938/cjmr20182630

JAK/STAT通路抑制剂对C57BL/6小鼠血清代谢组影响的¹H NMR研究

赵欣¹, 肖雄杰³, 高东莉³, 张先荣^1,2

1. 武汉大学基础医学院, 生理学系, 湖北武汉 430071;
2. 南方医科大学南方医院, 创伤骨科, 广东广州 510515;
3. 波谱与原子分子物理国家重点实验室, 武汉磁共振中心(中国科学院武汉物理与数学研究所), 湖北武汉 430071

收稿日期:2018-04-03 出版日期:2018-06-05 发布日期:2018-04-11
通讯作者: 张先荣,Tel:020-61641744,E-mail:xianrongzh@smu.edu.cn E-mail:xianrongzh@smu.edu.cn
基金资助:
国家自然科学基金资助项目（81573515）.

¹H NMR Study on Serum Metabonomic Alterations Induced by JAK/STAT Pathway Inhibitor in C57BL/6 Mice

ZHAO Xin¹, XIAO Xiong-jie³, GAO Dong-li³, ZHANG Xian-rong^1,2

1. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China;
2. Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
3. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan(Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences), Wuhan 430071, China

Received:2018-04-03 Online:2018-06-05 Published:2018-04-11

摘要/Abstract

摘要： JAK/STAT通路抑制剂已被应用于多种疾病的临床试验，但其全身性用药对机体组织细胞功能活性的影响目前尚不明确.本研究运用基于核磁共振氢谱（¹H NMR）的代谢组学方法分析了JAK/STAT通路抑制剂WP1066（20 mg/kg.bw，2天一次，持续2周）对C57BL/6小鼠血清代谢组的影响.首先采用¹H NMR技术检测了WP1066处理组和对照组小鼠血清的代谢物，然后对所得的图谱数据进行了主成分分析（PCA）以及正交偏最小二乘法分析（OPLS）.研究结果表明，抑制JAK/STAT通路可明显下调小鼠血清中的N-甲基烟酰胺（N-methylnicotinamide）水平，而上调顺乌头酸（cis-aconitate）、草酰乙酸（oxaloacetate）和乙酰胺（acetamide）水平，这些代谢物改变均与能量代谢密切相关.该结果提示代谢失衡相关指标可能作为JAK/STAT通路抑制剂治疗的临床监测参考指标.

关键词: 核磁共振(NMR), JAK/STAT通路抑制剂, 代谢组学, 能量代谢

Abstract: JAK/STAT pathway inhibitor has been used in clinic trial for several diseases. However, the adverse effect of systematic administration of JAK/STAT pathway inhibitors on cellular function is largely unknown. In the present study, alteration of metabolites in C57BL/6 mice serum were characterized using metabonomic analysis after WP1066 (a JAK/STAT pathway inhibitor) treatment (20 mg/kg.bw, once every 2 days for 2 weeks). ¹H NMR spectroscopy was used to detect the effect of WP1066 on metabolites component, and the metabolite profile were analyzed by principle component analysis (PCA) and orthogonal partial least squares (OPLS) analysis. Results showed that the level of N-methylnicotinamide was significantly downregulated, while cis-aconitate, oxaloacetate and acetamide were significantly upregulated in mice serum in response to JAK/STAT pathway inhibition. The above metabolic changes are associated with alterations in energy metabolism, indicating that parameters associated with metabolism unbalance may be used for monitoring the efficiency and adverse effect of JAK/STAT pathway inhibitor.

Key words: nuclear magnetic resonance (NMR), JAK/STAT pathway inhibitor, metabonomics, energy metabolism

中图分类号:

O482.53

赵欣, 肖雄杰, 高东莉, 张先荣. JAK/STAT通路抑制剂对C57BL/6小鼠血清代谢组影响的¹H NMR研究[J]. 波谱学杂志, 2018, 35(2): 198-203.

ZHAO Xin, XIAO Xiong-jie, GAO Dong-li, ZHANG Xian-rong. ¹H NMR Study on Serum Metabonomic Alterations Induced by JAK/STAT Pathway Inhibitor in C57BL/6 Mice[J]. Chinese Journal of Magnetic Resonance, 2018, 35(2): 198-203.

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JAK/STAT通路抑制剂对C57BL/6小鼠血清代谢组影响的¹H NMR研究

¹H NMR Study on Serum Metabonomic Alterations Induced by JAK/STAT Pathway Inhibitor in C57BL/6 Mice

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