泽泻在自发性高血压大鼠体内尿液代谢组学的研究

Study of Rhizoma alismatis on urine metabolism in spontaneously hypertensive rats

目的:考察泽泻对自发性高血压(SHR)大鼠干预前后的尿液代谢变化,寻找高血压病潜在标志物,探讨中药泽泻降压的药理机制。方法:基于UPLC-TOF/MS的代谢组学技术,将采集的SHR大鼠尿液样本进行单维及多维数据分析,鉴定差异化合物,分析相关代谢通路。结果:泽泻可平稳降压,干预前后大鼠的尿液代谢谱呈明显分离,干预前后L-酪氨酸、4-(2-氨基酚)-2,4-去酮丁酸、L-苯丙氨酸等8个标志物具有显著变化,涉及色氨酸代谢、酪氨酸代谢等芳香族氨基酸代谢通路。结论:SHR大鼠给予泽泻后可使异常的代谢趋向正常,并且其血压下降的机制可能与芳香族氨基酸代谢、脂质调节有关。

Objective： To investigate the changes of urine metabolism of Rhizoma alismatis before and after intervention in spontaneously hypertensive rats （SHRs）, find potential markers of hypertension, and explore the pharmacological mechanism of Rhizoma alismatis in reducing blood pressure. Methods： A High-performance liquid chromatography-time of flight/mass spectrography （UPLC-TOF/MS） method based metabolic profiling was employed to analyze the distinctive metabolic patterns of urine in SHRs. Statistic analyses were used to identify the discrepant compounds. Results： Rhizoma alismatis could depressurize steadily, and the urine metabolism spectrum of rats before and after the intervention was clearly separated. Eight markers of L-tyrosine, 4-（2-aminophenol）-2,4-deketine and L-phenylalanine had significant changes before and after the intervention, involving the metabolism of tryptophan, tyrosine metabolism, and other aromatic amino acid metabolic pathways. Conclusion： After giving Rhizoma alismatis to SHRs, abnormal metabolism tend to be normal, and the mechanism of its blood pressure decline may be related to aromatic amino acid metabolism and lipid regulation.