基于GC-TOF-MS代谢组学研究栝楼桂枝汤对脑缺血大鼠的作用机制

Based on GC-TOF-MS metabolomics to reveal the protective effect of Gua-Lou-Gui-Zhi Decoction against ischemic stroke in rats

目的研究栝楼桂枝汤对脑缺血中脑动脉闭塞(MCAO)模型大鼠的神经保护作用机制。方法运用气相色谱-飞行时间质谱联用的代谢组学技术及多元统计分析方法分析正常组、模型组和栝楼桂枝汤给药组大鼠血清中内源性代谢物的变化,筛选差异代谢物,并分析差异代谢物代谢途径。结果代谢组学研究结果显示各组间大鼠代谢谱出现显著差异,在大鼠血清质谱图中共筛选鉴定得吲哚乙酸、丙二酸、乙醇胺、肉豆蔻酸、鸟氨酸等13个差异代谢物,涉及的相关的代谢途径包括糖-葡萄糖醛酸相互转化途径,色氨酸代谢途径,嘧啶代谢和甘油磷脂代谢途径。结论栝楼桂枝汤可使造模后大鼠的体内代谢物有不同程度的恢复,其对缺血性脑卒中的保护作用主要反映在能量代谢、脂质代谢、氨基酸代谢等代谢途径的变化,改善大鼠脑缺血再灌注损伤症状。

Objective To investigate the protective effect of Gua-Lou-Gui-Zhi Decoction(GLGZD)on ischemic stroke in a middle cerebral artery occlusion(MCAO)rat model.Methods Gas chromatography-time of flight mass spectrometry(GC-TOF-MS)added with multivariate analyses was used to investigate the changes in serum endogenous metabolites in three group rats(normal group,model group and GLGZD group),to screen differential metabolites and their metabolic pathways.Results Metabolomic profiling showed a series of metabolic perturbation occurs in ischemic stroke compared with sham group.Thirteen differential metabolites such as indole acetic,malonic acid,ethanolamine,mycolic acid,ornithine etc.GLGZD can reverse the MCAO-induced serum metabolic deviations by regulating multiple metabolic pathways including interconversion of sugar and glucuronide,tryptophan metabolism,pyrimidine metabolism and glycerophospholipid metabolism.Conclusion To varying degrees,given GLGZD group rats can restore the metabolites in MCAO injury.Its protective effect on ischemic stroke mainly changes reflected in energy metabolism,lipid metabolism,amino acid metabolism pathway and reduce nerve cell-reperfusion injury in rats.