基于代谢组学的黄芩抗RSV肺炎作用机制研究  

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics

作　　者：贾明倩 高燕[2] 刘璐[2] 马露兰 陈曦 张悦[2] 王杨海 赵渤年 JIA Ming-qian;GAO Yan;LIU Lu;MA Lu-lan;CHEN Xi;ZHANG Yue;WANG Yang-hai;ZHAO Bo-nian(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Institute of Innovation in Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学药学院,山东济南250355 [2]山东中医药大学中医药创新研究院,山东济南250355

出　　处：《药学学报》2023年第7期1780-1789,共10页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划子课题(2017YFC1701501);山东省自然科学基金联合基金项目(ZR2021LZY021).

摘　　要：本研究基于UPLC-Q-Exactive HF X-MS的代谢组学技术探讨黄芩(Scutellaria baicalensis Georgi,SG)对呼吸道合胞病毒(respiratory syncytial virus,RSV)感染模型小鼠的改善作用,寻找可协助RSV肺炎诊断的生物标记物,分析黄芩发挥抗RSV活性的代谢途径。采用滴鼻感染RSV方法建立RSV肺炎小鼠模型,评价小鼠体重变化、肛温变化以及肺组织病理损伤。采集各组小鼠的肺组织样品,进行UPLC-Q-Exactive HF X-MS分析,通过代谢组学技术挖掘黄芩药物干预的差异性代谢物,并对黄芩调控的代谢通路进行分析。结果表明,黄芩能显著改善模型小鼠肺组织病理状态,使模型小鼠体重、肛温趋于正常;肺组织样本中,筛选出RSV模型小鼠疾病发展的生物标志物鸟嘌呤、L-天冬酰胺、花生四烯酸等46个,黄芩通过回调其中的尿酸、花生四烯酸、丙氨酸等22个潜在生物标志物发挥改善RSV感染作用,22个潜在标志物主要涉及11条异常代谢通路,其中与苯丙氨酸、酪氨酸和色氨酸生物合成,花生四烯酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢等5条代谢通路密切相关。黄芩主要通过调节氨基酸类、脂类、辅因子和维生素以及核苷酸类代谢物发挥改善RSV感染小鼠的作用。所有动物实验均在山东中医药大学动物伦理审查委员会的指导和批准下进行(批准号:SDUTCM20210311001)。This study,aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus(RSV)pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi(SG).,explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS.Mice models affected by RSV are established by nasal drip method and the changes of body weight,rectal temperature and pathological damage of lung tissue are evaluated.The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS.The differential metabolites of SG drug intervention are explored by metabolomics technology,and the metabolic pathways regulated by SG are analyzed.The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal.In the lung tissue samples,46 biomarkers,such as guanine,L-asparagine,and arachidonic acid,are screened for disease development in RSV model mice.SG improved RSV infection by recalling 22 potential biomarkers,such as uric acid,arachidonic acid,and alanine.The 22 potential markers mainly involved 11 abnormal metabolic pathways,including phenylalanine,tyrosine,and tryptophan biosynthesis,and arachidonic acid metabolism,alanine,aspartic acid and glutamate metabolism are closely related to the five metabolic pathways.SG improves RSV-infected mice mainly by regulating amino acids,lipids,cofactors and vitamins and nucleotide metabolites.All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine.(approval number:SDUTCM20210311001).

关 键 词：黄芩 呼吸道合胞病毒 代谢组学 作用机制 

分 类 号：R917[医药卫生—药物分析学]