Metabolomics Research Of Allergic Reaction Induced By Shli

Objective:We have established a metabolic method of rat for bovine serum albumin(BSA)induced by allergic reaction based on the technique of UPLC-Q-TOF-MS,to study the changes in endogenous metabolites between urines of rats in normal physiological conditions and bovine serum albumin,SHLI induced allergic reactions,identify potential biomarkers associated with allergic reactions,and then analyze the metabolic pathways and the metabolic mechanisms of allergic reactions induced by SHLI.METHODS:The bovine serum albumin-induced allergic reactions in rats were adopted as a model group,to simulate the symptoms of rat allergic reaction,The rats were randomly divided into two groups:control group and model group,we observed the systemic signs of performance in rats,the levels of tryptase and histamine in serum,,Pathological sections to comprehensively evaluate the rationality of animal models,then collected the rat urine,we used the UPLC-Q-TO F-MS to analyze the urine of rats,collected the UPLC-MS spectra in positive and negative ion mode,the chromatographic peaks were extracted and matched by Masslynx software,principal component analysis(PCA)and Partial Least Squares-Discriminant Analysis(PLS-DA)were used to analyze the dynamic changes of endogenous small molecule biomarkers in BSA-induced allergic reactions,to screen out the potential endogenous small molecule biomarkers associated with allergic reactions induced by BSA in the further.Based on the previously metabolomics model,The rats were randomly divided into four groups:control group,SHLI high dose group,SHLI medium dose group,SHLI low dose group,we tested the content of histamine and trypsin in rats,observed the pathological sections,then used metabolomics to analyze the urine of rats.The metabolic status of rats were analyzed by PCA and PLS-DA,analyzed the endogenous biomarkers and their metabolic pathways related to allergic reactions induced by SHLI,explore the allergic mechanism of SHLI allergic reactions at the metabolic level in the further.Results:This study established a metabolic method of rat allergic reaction model based on the UPLC-Q-TOF-MS technique,because of the administration of bovine serum albumin,the histamine and tryptase content has increased,at the same time,combined with the signs of the performance of rats and pathological sections has proved the success of the model;In this paper,by means of the metabolomics method in the further,we observed the control group and the model group have a more obvious clustering grouping,the content of endogenous bio markers in rats has a great changes after administration of bovine serum albumin,at the level of metabolomics also demonstrated that animal mode ls of allergic reactions were successful.14 kinds of potential biomarkers related to allergy were identified in the allergic reaction of rats model,these potential biomarkers may involve biosynthesis of isoflavone and folic acid and metabolism of tryptophan,nicotinic acid and nicotin-amide.In the allergic reaction of SHLI,compared to the control group,in the high dose group of SHLI and medium dose group of SHLI,the levels of histamine and tryptase were significantly increased and there was a significant difference,low dose group of SHLI has also increased,but there was not a significant difference.The pathological sections show that,degree of disease of the lung and trachea in rats has increased with the increase of the dosage.Based on the established metabolomics model,we found that the metabolomics map of SHLI groups has changed significantly,compared with the control group,the SHLI groups were significantly deviated,and there as a dose-dependent increase in distance between the control group and the SHLI high-dose group,and with the increase of the dose,the distribution of metabolic fluctuations were more obvious,identified 15 potential bio markers associated with SHLI-induced allergic reactions,these biomarkers may be associated with linolenic acid,phenylalanine,purine and other metabolic pathways.Conclusion:This study for the first time using metabolic methods to study the allergic reaction of SHLI,we established a urine metabolomics analysis platform of rats,to explore the mechanism of SHLI induced by allergic reactions,it laid the foundation for the safety research of SHLI and laid the experimental basis and method basis for the TCMI research at the same time.