基于代谢组学技术的麻黄汤对发热模型大鼠解热作用的初步研究

目的:基于超高效液相色谱-串联四级杆飞行时间二级质谱联用(UPLC-Q/TOF-MS)尿液代谢组学方法筛选麻黄汤干预模型大鼠的潜在生物标志物,探讨麻黄汤的解热作用机制。方法:取雄性Wistar大鼠24只,分为空白组、模型组、麻黄汤组。给药组给予麻黄汤(4.2 mL/kg),1 h后,模型组和给药组大鼠背部皮下注射20%干酵母混悬溶液(15 mL/kg)造模;收集造模后0,0~3,3~5,5~7,7~9,9~12,12~15和15~20 h各时间点的尿液,尿液样品进行UPLC-Q/TOF-MS检测分析,质谱数据采用MarkerLynx XS软件统计分析。结果:从尿样中分离出13种与发热有关的潜在生物标志物。鉴定了同丝氨酸、1-甲基腺苷、巴豆酰甘氨酸、黄嘌呤酸、6-羟基褪黑素、核黄素、5-甲氧基色氨酸、脱硫生物素、生物素、雌酮、2-甲氧基雌酮-3-葡萄糖醛酸酯、雄酮葡萄糖醛酸和7-酮脱氧胆酸代谢产物,这些代谢产物与生物素代谢、核黄素代谢、类固醇激素合成和色氨酸代谢途径紊乱有关,这有助于阐明麻黄汤的解热作用机制。结论:结果表明,麻黄汤对酵母菌诱导的大鼠发热模型具有一定的解热作用。

Preliminary Study on Antipyretic Effect of Mahuang Decoction on Febrile Model Rats Based on Metabonomics Technology

Objective:To investigate the antipyretic mechanism of Mahuang Decoction(MHD)by applying urine metabolomics method based on the ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)to screen out the potential metabolic markers in rats interfered by MHD.Methods:24 male Wistar rats were randomly divided into the blank group,the model group and the MHD group.The MHD group was orally administrated with Mahuang Decoction at a dose of 4.2 mL/kg.One hour later,the model group and the MHD group were injected with 20%aqueous suspension of yeast(15 mL/kg)to establish models.The urine of rats was collected during the period of 0,0~3,3~5,5~7,7~9,9~12,12~15 and 15~20 h,respectively.The urine samples were analyzed by UPLC-Q/TOF-MS and the urine mass spectrometry data were processed by MarkerLynx XS software.Results:13 potential metabolite biomarkers related to pyrexia were isolated from the urine specimens.The metabolites,such as homocitrulline,1-methyladenosine,tiglylglycine,xanthurenic acid,6-hydroxymelatonin,riboflavin,5-methoxytryptophan,dethiobiotin,biotin,estrone,2-methoxyestrone 3-glucuronide,etiocholanolone glucuronide and 7-ketodeoxycholic acid,were identified,and they were related to the disturbance of biotin metabolism,riboflavin metabolism,steroid hormone biosynthesis and tryptophan metabolism,which was helpful to understand the antipyretic action mechanism of MHD.Conclusion:These results indicated that MHD showed the significant antipyretic effect on rat model induced by yeast.