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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。
Metabolomics was used to study the changes of endogenous metabolites in the urine of bovine serum albumin-induced allergic rats and normal physiological rats, and the potential biomarkers associated with anaphylaxis were screened out, and their metabolic pathways were analyzed , To explore the metabolic mechanism of allergic reactions. The rat model of allergic reaction was induced by bovine serum albumin (BSA). Histamine and tryptase levels in rat serum were measured. The lung and trachea histomorphology were observed. By UPLC-Q-TOF-MS The urine of the allergic reaction model group and the blank control group were analyzed by the metabolomics method. The principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were used to observe the urine metabolism Contour differences, screening out different metabolites. There were significant differences in the metabolic profiles between the model group and the control group, and 14 differential metabolites and 4 major metabolic pathways related to anaphylaxis were screened out. This article established a urine metabolomics research method based on UPLC-Q-TOF-MS for bovine serum albumin-induced anaphylaxis and speculated that the mechanism of bovine serum albumin-induced anaphylaxis may involve isoflavone, folic acid Biosynthesis, tryptophan metabolism, niacin and nicotinamide metabolism and other processes for the further exploration of the application of metabolomics in the study of drug allergy lays the foundation.