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基于UPLC-Q-TOF-MS技术的牛血清白蛋白诱导过敏反应的代谢组学研究
引用本文:顾媛媛,张丹丹,冯程,王宇,陈大忠,王艳宏.基于UPLC-Q-TOF-MS技术的牛血清白蛋白诱导过敏反应的代谢组学研究[J].中国中药杂志,2016,41(21):4029-4035.
作者姓名:顾媛媛  张丹丹  冯程  王宇  陈大忠  王艳宏
作者单位:黑龙江中医药大学 中医药研究院, 黑龙江 哈尔滨 150040;哈尔滨医科大学 公共卫生学院, 黑龙江 哈尔滨 150086,黑龙江中医药大学 中医药研究院, 黑龙江 哈尔滨 150040,黑龙江中医药大学 中医药研究院, 黑龙江 哈尔滨 150040,黑龙江中医药大学 中医药研究院, 黑龙江 哈尔滨 150040,黑龙江中医药大学 中医药研究院, 黑龙江 哈尔滨 150040,黑龙江中医药大学 药学院, 黑龙江 哈尔滨 150040
基金项目:国家“重大新药创制”科技重大专项(2011ZX09201-201-15);黑龙江省应用技术研究与开发计划项目(GC13C109)
摘    要:运用代谢组学技术,研究牛血清白蛋白诱导过敏反应大鼠与正常生理状态大鼠尿液中内源性物质代谢的变化,筛选出与过敏反应相关的潜在生物标志物,进而分析其代谢通路,探讨过敏反应的代谢机制。采用牛血清白蛋白诱导大鼠发生过敏反应为模型,检测大鼠血清中组胺和类胰蛋白酶的含量,对大鼠肺和气管的组织形态学进行观察,通过UPLC-Q-TOF-MS技术对过敏反应模型组和空白对照组大鼠尿液进行代谢组学分析,采用主成分分析(PCA)和偏最小二乘辨别分析(PLS-DA)的方法,观察2组大鼠尿液的代谢轮廓差异,筛选出差异代谢物。模型组和对照组的代谢谱图存在明显差异,并筛选出与过敏反应相关的14个差异代谢物,4条主要代谢通路。该文建立了基于UPLC-Q-TOF-MS技术进行牛血清白蛋白诱导过敏反应的大鼠尿液代谢组学研究方法,推测牛血清白蛋白诱导过敏反应的作用机制可能涉及异黄酮、叶酸的生物合成,色氨酸代谢、烟酸和烟酰胺代谢等过程,为进一步探索代谢组学在药物过敏反应研究中的应用奠定了基础。

关 键 词:牛血清白蛋白  生物标志物  代谢组学  过敏反应
收稿时间:2016/6/17 0:00:00

Metabolomics of bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS
GU Yuan-yuan,ZHANG Dan-dan,FENG Cheng,WANG Yu,CHEN Da-zhong and WANG Yan-hong.Metabolomics of bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS[J].China Journal of Chinese Materia Medica,2016,41(21):4029-4035.
Authors:GU Yuan-yuan  ZHANG Dan-dan  FENG Cheng  WANG Yu  CHEN Da-zhong and WANG Yan-hong
Institution:Institute of Traditional Chinese Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China;Institute of Public Health, Harbin Medical University, Harbin 150086, China,Institute of Traditional Chinese Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China,Institute of Traditional Chinese Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China,Institute of Traditional Chinese Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China,Institute of Traditional Chinese Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China and Institute of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China
Abstract:The metabonomic techniques were used to study the changes in endogenous metabolites between urines of rats in normal physiological conditions and bovine serum albumin induced allergic reactions, identify potential biomarkers associated with allergic reactions, and then analyze the metabolic pathways and the metabolic mechanisms of allergic reactions. The bovine serum albumin-induced allergic reactions in rats were adopted as a model to detect histamine and tryptase in rat serum and observe the issue morphology of lungs and trachea in rats. UPLC-Q-TOF-MS was applied in metabonomic analysis on urines between control group and allergic reaction model group. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were applied to observe the differences in metabolic profiling between urines of the two groups and select differential metabolites. There were significant differences in metabolism spectrum between the model group and the control group. Totally 14 differential metabolites and 4 major metabolic pathways were screened out. The metabonomic research method for urines of rats with bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS was established in this study. It was speculated that the mechanism of bovine serum albumin-induced allergic reactions may involve biosynthesis of isoflavone and folic acid and metabolism of tryptophan, nicotinic acid and nicotinamide. It lays a foundation for further exploration of the application of metabolomics in drug allergy reaction studies.
Keywords:bovine serum albumin  biomarker  metabolomics  allergic reaction
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