顾媛媛+张丹丹+冯程+王宇+陈大忠+王艳宏

[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

[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.

[Key words]bovine serum albumin； biomarker； metabolomics； allergic reaction

doi：10.4268/cjcmm20162123

過敏反应又称变态反应，是指机体受同一抗原再次刺激后产生的一种异常或病理性免疫反应，主要表现为生理功能紊乱和组织损伤。过敏反应是临床常见的不良反应，大多数药物都有可能引起过敏反应，严重影响人类的健康，其危害不容忽视。……