基于粪便代谢物组学分析麻黄细辛附子汤干预H1N1流感病毒感染小鼠的作用机制  

Mechanism Analysis of Mice Model with H1N1 Influenza Virus Intervened by Mahuang Xixin Fuzi Tang Based on Fecal Metabolomics

作　　者：李灿[1] 孙启慧 付业佩 巩丽丽[1] 杨勇[1] 蒋海强[1] 容蓉[1] 

机构地区：[1]山东中医药大学,济南250355

出　　处：《中国实验方剂学杂志》2017年第9期74-79,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81273626);国家"重大新药创制"科技重大专项(2014ZX09509001-001);山东省重点研发计划项目(2016YJS08A01-5)

摘　　要：目的:运用代谢组学方法研究麻黄细辛附子汤(Mahuang Xixin Fuzi Tang,MXF)干预H1N1流感病毒感染小鼠粪便样品中内源性物质的变化,寻找与疾病相关的生物标志物,探讨MXF干预H1N1流感病毒感染可能的作用机制。方法:将30只KM小鼠随机等分为空白组、模型组和MXF组,小鼠滴鼻感染H1N1流感病毒后灌服MXF(给药剂量20 m L·kg^(-1)),模型组和空白组灌服等量水,连续给药7 d并测量各组小鼠的体重和肛温,收集各组小鼠的粪便。采用Halo C_(18)色谱柱(2.1 mm×100 mm,2.7μm),流动相0.05%甲酸水溶液-0.05%甲酸乙腈溶液梯度洗脱,质谱扫描范围m/z 80~1 200,对粪便样品进行LC-MS测定并结合主成分分析和偏最小二乘判别分析寻找潜在生物标志物。结果:空白组、模型组和MXF组代谢模式显著不同,鉴定出了9个潜在生物标志物,分别为磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰胆碱、溶血磷脂酰胆碱、吡哆醛、草酰乙酸、琥珀酸、褪黑素和L-犬尿氨酸。结论:MXF干预H1N1流感病毒感染的机制可能与其对色氨酸代谢、维生素B6代谢、甘油磷脂代谢和三羧酸循环等代谢紊乱的回调作用有一定相关性。Objective： To analyze the endogenous metabolite changes in the fecal supernatant of mice infected with H1N1 influenza virus and intervened by Mahuang Xixin Fuzi Tang（ MXF）, and to explore the therapeutic mechanism of MXF through metabolomics technology. Method： KM mices were randomly divided into blank group,model group and MXF group,modle mice were intranasally inoculated with H1N1 influenza virus,and then intervened by MXF（ dose of 20 m L·kg^-1） through orally administration. All drug treatments were administered daily for consecutive 7 days, body weight and rectal temperature were measured, the feces were collected. Ultra performance liquid chromatography coupled to Q-exactive high resolution mass spectrometry analysis was prformed on a Halo C_（18）column（ 2. 1 mm × 100 mm,2. 7 μm） with 0. 05% formic acid in water and 0. 05% formic acid in acetonitrile for gradient elution as mobile phase and the mass spectral scanning range of m / z80-1 200. LC-MS data were processed with principal components analysis（ PCA） and partial least squares discriminant analysis（ PLS-DA） to find out potential biomarkers. Result： Significant differences were found in the metabolic profiles among the blank group, model group and MXF group. Nine metabolites were identified as potential biomarkers, such as phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, lysophosphatidylcholine,L-kynurenine,oxalacetic acid,pyridoxal,succinic acid and melatonin. Conclusion： The flu induced by H1N1 virus may interfere with the typophan,vitamin B6,glycerol phospholipids and tricarboxylic acid cycle metabolic pathway according to these identified biomarkers. MXF may play a therapeutic role in a way of regulating the above disordered metabolic pathways.

关 键 词：麻黄细辛附子汤 代谢组学 粪便 H1N1流感病毒 维生素B6 生物标志物 色氨酸 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]