Urinary UPLC-MS metabolomics dissecting the underlying mechanisms of Huaxian capsule protects against sepsis
Urinary UPLC-MS metabolomics dissecting the underlying mechanisms of Huaxian capsule protects against sepsis
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DOI：
10.1039/c6ra07987c
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Zhang, Ai-Hua
中科院分区：
文献类型：
--
作者：
Liang, Qun;Liu, Han;Zhang, Ai-Hua
严重脓毒症（SS）仍然是一个全球性的威胁，不仅在工业化国家，而且在发展中国家。目前，SS的发病率呈上升趋势，且缺乏有效的治疗药物。化纤胶囊是治疗SS的传统中药。本研究旨在探讨活血胶囊治疗SS的药理作用机制。代谢组学是研究代谢表型、潜在代谢物生物标志物和代谢途径的有力工具。在这里，我们通过进行代谢谱和代谢物生物标志物研究了SS大鼠的代谢变化。尿UPLC-MS结合多变量统计分析，包括主成分分析（PCA），偏最小二乘判别分析（PLS-DA）和正交投影潜在结构判别分析（OPLS-DA），用于评估表型变化。采用无监督主成分分析法，对对照组、SS组和HXC组进行识别。使用MetPA网络工具进行代谢途径分析。结果表明，SS大鼠尿中10种潜在的代谢物生物标志物涉及苯丙氨酸、酪氨酸和色氨酸的生物合成，缬氨酸、亮氨酸和异亮氨酸的生物合成，甘氨酸、丝氨酸和苏氨酸的代谢，酪氨酸的代谢途径。无监督PCA评分图显示，活血胶囊组调节代谢动态变化的聚类较模型组聚类更接近对照组，说明活血胶囊对SS大鼠有治疗作用。总体而言，这表明尿UPLC-MS代谢组学可以剖析HXC保护SS的潜在机制。
Severe sepsis (SS) remains a worldwide threat, not only in industrialized countries but also in developing countries. Currently, the incidence of SS is rising, and there is a lack of effective drugs. Huaxian capsule (HXC) is traditional Chinese medicine with therapeutic effects on SS. The objectives of this study were to explore the underlying mechanisms of pharmacological effects of HXC on the treatment of SS. Metabolomics is a powerful tool for the characterization of metabolic phenotypes, potential metabolite biomarkers and metabolic pathways. Here, we investigated the metabolic changes in SS rats by performing metabolic profiling and metabolite biomarkers. Urinary UPLC-MS coupled with multivariate statistical analysis including principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to assess phenotypic changes. Metabolites contributing to the discrimination the control group, SS group and HXC group were identified by using unsupervised PCA. Metabolic pathway analysis was performed using the MetPA web tool. As a result, 10 potential metabolite biomarkers in urine involved phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, tyrosine metabolism pathways, were identified in SS rats. The unsupervised PCA score plot showed that the HXC group cluster modulating dynamic metabolic changes was closer to that of the control group than the model group cluster, demonstrating that HXC has therapeutic effects on SS rats. Overall, it showed that urinary UPLC-MS metabolomics could dissect the underlying mechanisms of HXC protects against SS.