药学学报, 2015, 50(7): 875-881
杨雯晴, 李运伦, 蒋海强. 基于高效液相色谱-质谱技术的缬沙坦作用机制的研究[J]. 药学学报, 2015, 50(7): 875-881.
YANG Wen-qing, LI Yun-lun, JIANG Hai-qiang. The mechanism of action of valsartan studied by HPLC-TOF/MS[J]. Acta Pharmaceutica Sinica, 2015, 50(7): 875-881.

杨雯晴1, 李运伦2, 蒋海强1
1. 山东中医药大学, 山东 济南 250355;
2. 山东中医药大学附属医院, 山东 济南 250011
采用高效液相色谱-质谱技术 (HPLC-TOF/MS), 并结合SIMCA-P软件进行偏最小二乘判别分析, 研究缬沙坦干预后大鼠血清内源性代谢物变化, 寻找其潜在生物标记物, 并利用MetPA平台鉴别缬沙坦在干预机体过程中相关的代谢通路, 以探索缬沙坦治疗高血压病的作用机制。结果显示, 给予缬沙坦连续干预4周后收缩压降低效果明显 (P < 0.05); 缬沙坦干预后自发性高血压大鼠 (SHR) 血清代谢模式发生改变, 鉴定出4种代谢产物及其相关代谢通路, 这些代谢产物与G蛋白偶联通路密切相关。本文提示代谢组学关注药物进入机体后的整体改变和微观转化, 从而可以在阐明药物作用机制方面发挥积极的作用。
关键词:    代谢组学      缬沙坦      HPLC-MS     
The mechanism of action of valsartan studied by HPLC-TOF/MS
YANG Wen-qing1, LI Yun-lun2, JIANG Hai-qiang1
1. Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
2. The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China
High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
Key words:    metabonomics    valsartan    HPLC-MS   
收稿日期: 2014-11-15
基金项目: 国家自然科学基金面上项目 (81273700).
通讯作者: 李运伦
Email: li.yunlun@163.com
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