中国中药杂志

2017, v.42(04) 763-771

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基于代谢组学的麻黄细辛附子汤治疗流感小鼠的作用机制研究
Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information

孙启慧;张静;李壮壮;杜宝香;蒋海强;杨勇;吕青涛;容蓉;
SUN Qi-hui;ZHANG Jing;LI Zhuang-zhuang;DU Bao-xiang;JIANG Hai-qiang;YANG Yong;LV Qing-tao;RONG Rong;Shandong University of Traditional Chinese Medicine;

摘要(Abstract):

该研究运用代谢组学方法,研究麻黄细辛附子汤(MXF)干预的流感小鼠血清中内源性代谢物的变化,寻找潜在生物标志物及相关的代谢通路,探讨MXF的药效及作用机制。实验选用昆明(KM)小鼠36只,随机分为正常组、流感组、MXF组,使用流感病毒H1N1滴鼻感染,建立流感小鼠模型;MXF组使用药物干预,其他组给予等体积的生理盐水,每日1次,连续6 d,记录小鼠的体重、肛温等药理指标,末次给药24 h后收集血清样本,采用HPLC-TOF-MS检测。结果显示,与正常组相比,流感组小鼠体重、肛温均出现不同程度下降,肺指数和死亡率明显升高(P<0.05),MXF组各药理指标出现良好的回调趋势;血清样本采集的原始数据,使用R语言,MPP,SIMCA-P等软件进行处理,发现3组小鼠血清中14种内源性物质发生显著性变化(P<0.05),经MXF干预后代谢物水平均出现不同程度的回调;进一步利用Met PA数据平台分析发现,14种代谢物涉及的通路包括糖代谢、花生四烯酸代谢、甘油磷脂和鞘脂代谢等。通过对这些差异性代谢物生理功能的分析,并结合测定的宏观药理指标的分析,推测MXF可能从改善糖代谢,调节花生四烯酸代谢、甘油磷脂和鞘脂代谢等多途径,发挥其药效作用。
This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction( MXF) based on metabolomics method,investigate potential biomarkers and related metabolic pathways,and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming( KM) mice were randomly divided into three groups: normal group,model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation,and the other two groups were given with equal volume of saline solution in the same way. Body weight,rectal temperature,morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group,the body weight and rectal temperature were decreased in model group,and their lung index and mortality rate were significantly increased( P < 0. 05); MXF had good therapeutic effects on the abnormity of body weight,rectal temperature,lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language,MPP,SIMCA-P and other software,and significant changes were found in 14 kinds of endogenous substances from mice serum( P < 0. 05). As compared with model group,the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with Met PA data platform showed that,the pathways involved in 14 metabolites included glucose metabolism,arachidonic acid metabolism,glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism,regulating arachidonic acid metabolism,glycerophospholipid and sphingolipid metabolic pathways.

关键词(KeyWords): 代谢组学;流感小鼠模型;麻黄细辛附子汤;潜在生物标志物
metabolomics;mice model infected with influenza virus A;Mahuang Xixin Fuzi decoction;potential metabolic markers

Abstract:

Keywords:

基金项目(Foundation): 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(2016CYJS08A01-5)

作者(Author): 孙启慧;张静;李壮壮;杜宝香;蒋海强;杨勇;吕青涛;容蓉;
SUN Qi-hui;ZHANG Jing;LI Zhuang-zhuang;DU Bao-xiang;JIANG Hai-qiang;YANG Yong;LV Qing-tao;RONG Rong;Shandong University of Traditional Chinese Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20170103.022

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