基于UPLC/LTQ-Orbitrap-MS的消风宣窍汤对变应性鼻炎小鼠尿液代谢组学研究

Urine Metabonomic Study on Xiaofeng Xuanqiao Decoction in Treatment of Anaphylactic Rhinitis Based on UPLC/LTQ-Orbitrap-MS

目的分析变应性鼻炎(Allergic rhinitis,AR)模型小鼠尿液内源性代谢物的变化,观察消风宣窍汤对AR异常代谢物的调节作用,从代谢组学的角度探究消风宣窍汤作用机制。方法将60只BALB/c小鼠随机分为对照组、模型组、孟鲁司特组和消风宣窍汤组,以卵蛋白腹腔注射进行致敏,局部鼻黏膜激发的方法建立BALB/c小鼠AR模型,孟鲁司特组和消风宣窍汤组分别给予孟鲁司特钠片和消风宣窍汤,每天2次,连续7d,各组分别于给药最后1天采集尿液样本。采用基于UPLC/LTQ?Orbitrap-MS的代谢组学技术研究各组代谢物的变化,分析药物的干预机制。结果 AR引起小鼠体内酸类、胺类等多种代谢物紊乱。消风宣窍汤主要调控了其中14种异常代谢物的水平,对AR小鼠的干预效果良好。结论 AR小鼠尿液中多个小分子偏离正常状态,消风宣窍汤主要通过对非对称性二甲基精氨酸(ADMA)、N-甲基烟酸、S-腺苷甲硫氨酸(SAMe)、吲哚-2-羧酸(I2CA)、6-氨基己酸(EACA)、咪唑乙酸、1-甲基-4-吡啶-5-羧酰胺(M4PY)的上调和1-甲基组胺的下调,改善组氨酸代谢和半胱氨酸和蛋氨酸代谢以达到治疗效果。

OBJECTIVE To observe the regulation of Xiaofeng Xuanqiao Decoction(XFTQ)on abnormal metabolites by analyzing the changes of endogenous metabolites in urine of anaphylactic rhinitis(AR)mice,and to explore the mechanism of Xiaofeng Xuanqiao Decoction on treating AR from the perspective of metabonomics.METHODS 60 BALB/c mice were divided into normal group,model group,montelukas group and XFTQ group.Intraperitoneal injection of OVA and local nasal mucosa stimulation was used to establish AR model.Montelukast group and XFTQ group were given montelukast sodium tablets and Xiaofeng Xuanqiao decoction,respectively,for 7 d.Urine samples were collected from each group on the last day of administration.UPLC/LTQ-Orbitrap-MS was applied to analyze the metabolic profile changes of each group and the intervention mechanism of drugs.RESULTS AR disordered the metabolism of acid,amine and others in mice.Xiaofeng Decoction mainly regulated the levels of 14 kinds of abnormal metabolites,and it showed good intervention effect on AR mice.CONCLUSIONSmall molecule metabolites in AR mice are deviated from the normal group.Xiaofeng Xuanqiao Decoction improves the histidine metabolism and cysteine and methionine metabolism to achieve therapeutic effect,mainly through the up-regulation of asymmetric dimethyl-arginine(ADMA),N-methylnicotinic acid,S-adenosyl-L-methionine(SAMe),indole-2-carboxylic acid(I2 CA),6-aminocaproic acid(EACA),imidazole-4-acetic acid,1-methyl-4-pyridone-5-carboxamide(M4 PY),and the down-regulation of 1-methylhistamine.