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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
作者姓名:郭双  戴成球  金钦  张玉琴  许文  黄鸣清  林羽  徐伟
作者单位:福建中医药大学药学院,福建福州350122;福建中医药大学生物医药研发中心,福建福州350122;福建中医药大学药学院,福建福州350122
基金项目:国家自然科学基金(No.81673561、81674046、81503204);福建中医药大学校管课题(No.X2017009-平台);福建省高校新世纪优秀人才支持计划(No.闽教科2015);福建省高校杰出青年科研人才计划(No.闽教科2016)
摘    要:目的 研究栝楼桂枝汤对脑缺血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。

关 键 词:栝楼桂枝汤  代谢组学  气相色谱-高分辨率飞行时间质谱  中脑动脉闭塞大鼠

GC-MS-based metabolomics to reveal the protective effect of Gua-Lou-Gui-Zhi decoction against ischemic stroke in rat
Authors:GUO Shuang  DAI Chengqiu  JIN Qin  ZHANG Yuqin  XU Wen  HUANG Mingqing  LIN Yu and XU Wei
Institution:1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China,1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China and 1.School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;2.Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China
Abstract:Objective To investigated 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 rat (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 rat 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.
Keywords:Gua-Lou-Gui-Zhi decoction  Metabolism  GC-TOF-MS  MCAO rat
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