药学学报, 2019, 54(8): 1476-1483
杜珂, 高晓霞, 冯彦, 张斌, 王佩义, 秦雪梅. 基于血清代谢组学的龟龄集改善大鼠肾阳虚证作用研究[J]. 药学学报, 2019, 54(8): 1476-1483.
DU Ke, GAO Xiao-xia, FENG Yan, ZHANG Bin, Wang Pei-yi, QIN Xue-mei. Effects of Guilingji on Kidney-Yang deficiency syndrome in rats based on serum metabolomics[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1476-1483.

杜珂1,2, 高晓霞1, 冯彦1,2, 张斌3, 王佩义3, 秦雪梅1
1. 山西大学中医药现代研究中心, 山西 太原 030006;
2. 山西大学化学化工学院, 山西 太原 030006;
3. 山西广誉远国药有限公司, 山西 太谷 030800
分析龟龄集(Guilingji,GLJ)对氢化可的松致肾阳虚证大鼠血清内源性代谢物紊乱的调控作用,明确其发挥药效的代谢调控通路。以大剂量注射氢化可的松复制大鼠肾阳虚证模型。将大鼠随机分为对照组、模型组、阳性药(金匮肾气丸)组和龟龄集低、中、高剂量组,连续给药30天。利用传统药效学指标(体质量、行为学、生化指标)评价龟龄集药效。动物实验获得山西大学伦理委员会的批准。采用基于UHPLC-Q Exactive Orbitrap-MS代谢组学方法研究血清的整体代谢轮廓,分析龟龄集改善肾阳虚证的代谢调控机制。结果显示,龟龄集可显著改善肾阳虚证;通路分析显示亮氨酸-异亮氨酸代谢、醚酯代谢、胆汁酸代谢为其改善肾阳虚证的主要途径;龟龄集对肾阳虚证改善作用的主要效应机制涉及其对能量平衡、肠道稳态和免疫功能的调节作用。
关键词:    龟龄集      肾阳虚证      血清      代谢组学      通路分析     
Effects of Guilingji on Kidney-Yang deficiency syndrome in rats based on serum metabolomics
DU Ke1,2, GAO Xiao-xia1, FENG Yan1,2, ZHANG Bin3, Wang Pei-yi3, QIN Xue-mei1
1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China;
2. College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China;
3. Shanxi Guangyuyuan Traditional Chinese Medicine Co., Ltd., Taigu 030800, China
This study aimed to address the protective role of Guilingji (GLJ) against hydrocortisone-induced Kidney-Yang deficiency syndrome in rats with metabolites in serum, and explore its regulative approaches. KidneyYang deficiency syndrome rat model was constructed by high-dose injection of hydrocortisone. Rats were randomly divided into 6 groups:control group, model group, positive (Jinkui Shenqi Wan) group and low, medium, or highdose group of GLJ for continuous administration over 30 days. The efficacy of GLJ was evaluated with traditional pharmacodynamic indicators (body weight, behavioral indicators, and biochemical parameters) after the model was replicated successfully. Animal experimentation was approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. Serum metabolic profiles obtained by UHPLC-Q Exactive Orbitrap-MS were used to explore metabolic regulation mechanism of GLJ. The results showed that GLJ could significantly improve Kidney-Yang deficiency syndrome. Pathway analysis showed that leucine-isoleucine metabolism, ether ester metabolism, and bile acid metabolism were the main pathways, with the main mechanism of action involving energy balance, intestinal homeostasis and immune function.
Key words:    Guilingji    Kidney-Yang deficiency syndrome    serum    metabolomics    pathway analysis   
收稿日期: 2019-04-22
DOI: 10.16438/j.0513-4870.2019-0310
基金项目: 山西省科技重点研发计划(201603D3113006);山西省重点实验室项目(201605D111004);山西省科技创新重点团队(201605D131045-18).
通讯作者: 秦雪梅,Tel:86-351-7011501,E-mail:qinxm@sxu.edu.cn
Email: qinxm@sxu.edu.cn
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杜珂  在本刊中的所有文章
高晓霞  在本刊中的所有文章
冯彦  在本刊中的所有文章
张斌  在本刊中的所有文章
王佩义  在本刊中的所有文章
秦雪梅  在本刊中的所有文章

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