基于超高效液相色谱-四极杆飞行时间串联质谱的急性过敏反应代谢组学研究

目的: 利用代谢组学的方法研究牛血清白蛋白诱导的豚鼠急性过敏反应模型,寻找能够表征该模型的尿液代谢物中的生物标记物。 方法: 采用基于超高效液相色谱-四极杆飞行时间串联质谱(UPLC-QTof-MS)的代谢组学技术,并结合主成分分析(PCA)和偏最小二乘辨别分析(PLS-DA)的方法,研究正常豚鼠和急性过敏反应组豚鼠尿液代谢物的变化。 结果: 牛血清白蛋白诱导豚鼠发生强阳性过敏反应。急性过敏反应组与正常对照组豚鼠存在明显的代谢差异,通过查询KEGG数据库确定了4个化合物的结构及代谢途径,包括谷胱甘肽、正辛酸、甲硫基庚基苹果酸和AL-321。 结论: 代谢组学方法能用于牛血清白蛋白诱导的豚鼠急性过敏反应模型研究,为进一步探索代谢组学在药物急性过敏反应研究中的应用奠定了基础。

Objective: To conduct UPLC-QTof/MS urine metabolic profiling of anaphylaxis animal model and look for potential biomarkers in urine metabolites to characterize anaphylaxis. Methods: Combined with the principal component analysis(PCA)and partial least squares-diacriminant analysis(PLS-DA),the major metabolic changes in urine between the normal and anaphylaxis model guinea pigs were detected by UPLC-QTof/MS. Results: Typical clinical symptoms appeared after the animals had been administrated with cattle albumin.Clustering trend of two groups based on variables was observed and four compounds of the structure and metabolic pathways had been confirmed through inquiring KEGG Database,including GSH,caprylic acid,methylthio-heptylmalic acid and AL-321. Conclusion: UPLC-QTof/MS based metabolic profiling analysis can be an effective auxiliary tool for investigation of anaphylaxis,which laid a foundation to further applying metabolomics study to acute anaphylaxis.

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