A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry
A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry
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UPLC/LTQ-Orbitrap质谱法研究金欣口服液对RSV感染小鼠影响的代谢组学方法
DOI：
10.1016/j.jep.2015.07.040
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发表时间：
2015-11-04
影响因子：
5.4
通讯作者：
Wang, Shou-chuan
中科院分区：
文献类型：
--
作者：
Du, Li-na;Xie, Tong;Wang, Shou-chuan
民族药理相关性：金心口服液(JOL)是一种由麻杏石甘汤改进而成的中药配方，是一种古老的配方，广泛用于治疗呼吸系统疾病，如支气管炎、肺炎和哮喘。在我们以往的研究中，Jol被证明安全有效地治疗病毒性肺炎，特别是涉及呼吸道合胞病毒(RSV)的肺炎。目的：为了探讨Jol对RSV感染小鼠的作用机制，采用基于超高效离子陷阱四极杆轨道质谱仪的代谢组学方法(UPLC/LTQ-Orbitrap-MS)。材料和方法：Balb/c小鼠分为4组，对照组(生理盐水接种/不治疗)、RSV接种/生理盐水治疗组(RSV接种/Jol治疗)、RSV+Jol组(RSV接种/病毒组)和RSV+Riba组(RSV接种/病毒组)。接种/治疗7d后采集血浆和肺组织标本，建立基于代谢组学的UPLC/LTQ-Orbitrap-MS方法。主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)用于筛选可能与JOL抗RSV活性相关的生物标志物。结果：JOL与RSV感染肺组织的炎症反应降低有关。PCA和OPLS-DA的结合显示，RSV诱导的血浆和肺组织中的11个生物标记物和16个生物标记物的偏差经JOL处理后得到纠正。这些生物标记物主要是甘油磷胆碱、鞘磷脂和甘油脂代谢途径的组成部分。Jol可使RSV感染小鼠血浆和肺组织中这些生物标志物的异常水平恢复到接近正常水平。结论：Jol可有效治疗RSV肺炎，其部分机制可能是通过改善相关的脂代谢紊乱来实现的。这一结果为进一步阐明JOL抗RSV的作用机制提供了依据，同时也证明了代谢组学是研究中医药治疗RSV肺炎疗效及其相关生物标志物的有价值的工具。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV).Aim of the study: To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS).Materials and methods: BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL.Results: JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels.Conclusions: This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved. (c) 2015 Elsevier Ireland Ltd. All rights reserved.