采用代谢组学策略研究佛手散对急性血瘀大鼠的活血化瘀作用机制

采用冰水浴游泳和皮下注射盐酸肾上腺素法复制急性血瘀大鼠模型。采用UPLC-Q-TOF/MS方法分析正常大鼠、急性血瘀大鼠和给药佛手散干预急性血瘀大鼠尿液之间的内源性代谢物差异,并通过变量重要性投影选取潜在的生物标志物,结合质谱信息和数据库检索对潜在的生物标志物进行鉴定,将鉴定到的生物标志物输入MetPA数据库中构建代谢通路。研究急性血瘀大鼠给药佛手散后大鼠尿液内源性代谢物变化,寻找可能的生物标志物,探讨佛手散的活血化瘀作用机制。结果在急性血瘀大鼠尿液中发现并鉴定了11个潜在的生物标志物,这些标志物主要和苯丙氨酸代谢、色氨酸代谢和鞘脂类代谢3条代谢通路相关。而佛手散可调节急性血瘀模型大鼠体内紊乱的代谢通路并使其向正常状态转归。该研究结果表明代谢组学在中药整体性药效评价、作用机制的阐明等方面具有很好的应用前景。

Evaluate activating blood circulation and dissipating blood stasis effect mechanism of Foshousan on acute blood stasis rats on basis of metabolomic approach

Ice water bath and subcutaneous injection of adrenaline were used to establish the acute blood stasis model of rats. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to study the urine metabolic changes of acute blood stasis rats. Potential biomarkers were selected by variable importance projection, and identified on basis of MS information and databases. The metabolic pathways were predicted via MetPA database. To study the effect of Foshousan on endogenous metabolites of acute blood stasis model rats, find potential biomarkers, and explore the effect mechanism of Foshousan on activating blood circulation and dissipating blood stasis. Eleven potential biomarkers were identified with multivariate statistical analysis of urine metabolite profiles, and which also were used to explain the phenylalanine metabolism, tryptophan metabolism and sphingolipid metabolism. Those disturbed metabolic pathways in acute blood stasis rats could be regulated closely to normal state after Foshousan administration. Metabolomics has a bright prospect in the efficacy evaluation and effect mechanism elucidation of the traditional Chinese medicines.