Abstract: Objective LC-TOF-MS was used to analyze the plasma of the experimental group of spontaneously hypertensive rats ( SHR, Wistar Kyoto) and the control group of Wistar ( WKY, Wistar Kyoto) rats. To explore the characteristic biomarkers and metabolic pathways of SHR by using metabolomics method. Method Plasma samples from SHR and WKY rats were collected, and endogenous metabolites in plasma were separated by reversed-phase chromatography ( RPLC ) and hydrophilic interaction chromatography ( HILIC ) , The data was analyzed by partial least squares discriminant analysis ( PLS-DA) . Result A good separation trend was observed between the SHR experimental group and the WKY rat control group in HILIC and RPLC modes. Identified 17 potential compounds including histidine, proline, uric acid, pyroglutamic acid, acetylcarnitine, palmitoylcarnitine, dihydrosphingosine, 3-dehydrosphingosine among SHR biomarkers, the main disturbed metabolic pathways are the carnitine shuttle system and sphingolipid metabolism. Conclusion The affected biomarkers and metabolic pathways provide evidence for understanding the metabolic mechanisms of hypertension.

Key words: hypertension, biomarkers, liquid chromatography-mass spectrometry, metabolomics

摘要： 目的 利用液质联用系统( LC-TOF-MS) 对自发性高血压大鼠( SHR) 实验组和京都种 Wistar( WKY,Wistar Kyoto)大鼠对照组的血浆进行分析,利用代谢组学方法探寻 SHR 的特征性生物标志物及代谢途径。 方法 收集 SHR 和 WKY 大鼠(各 12 只)的血浆样本,利用反相色谱(RPLC)和亲水相互作用色谱 ( HILIC) 分离血浆中的内源性代谢物,利用偏最小二乘法判别分析( PLS-DA)法进行数据分析。 结果 在 HILIC 和 RPLC 模式下 SHR 实验组和 WKY 大鼠对照组之间观察到了良好的分离趋势。 鉴定出了包括组氨酸、脯氨酸、尿酸、焦谷氨酸、乙酰肉碱、棕榈酰肉碱、二氢鞘氨醇、3-脱氢鞘氨醇等 17 个潜在的 SHR 生物标志物,主要受干扰的代谢途径是氨基酸代谢、肉碱穿梭系统和鞘脂代谢。 结论 受到影响的生物标志物和代谢途径可为理解高血压的代谢机制提供依据。

关键词: 高血压, 生物标志物, 液相色谱-质谱, 代谢组学