High-throughput and multi-dimensional omics approach uncovers a huaxian capsule to ameliorate the dysregulated expression profiling of severe sepsis rats

High-throughput and multi-dimensional omics approach uncovers a huaxian capsule to ameliorate the dysregulated expression profiling of severe sepsis rats
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DOI:
10.1039/c6ra28337c
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发表时间:
2017-01-01
期刊:
影响因子:
3.9
通讯作者:
Ai, Huazhang
Ai, Huazhang
中科院分区:
化学3区
文献类型:
--
作者:
Liang, Qun;Liu, Han;Ai, Huazhang

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多维组学可能有助于解释疾病的潜在机制。严重脓毒症(SS)是重症监护病房死亡和发病的主要原因,由于缺乏有效的药物,给医疗保健带来了巨大的负担。SS的潜在病理生理学也鲜为人知。华仙胶囊是一种治疗SS的中草药制剂。在这里,我们旨在通过代谢谱和生物标志物分析来研究SS大鼠的代谢变化。采用UPLC/MS和化学计量学相结合的方法评价细胞的表型反应。结果,我们鉴定了12个潜在的代谢物生物标志物,它们参与了多种代谢途径的失调,如甘油磷脂代谢、类固醇激素的生物合成、鞘脂代谢紊乱等。然后,我们进行了microRNA分析,结果表明HXC改善了SS的失调表达谱。与模型组相比,我们鉴定出56个差异表达的miRNAs,其中20个表达下调,36个表达上调。这项研究表明,microRNA和代谢谱是探索草药代谢反应的有价值的方法,并可以加深我们对SS治疗的分子基础的理解。
Multi-dimensional omics could be helpful to interpret the underlying mechanisms of disease. Severe sepsis (SS) is a major cause of mortality and morbidity in intensive care units and has a large burden on healthcare due to a lack of effective drugs. The underlying pathophysiology of SS is also poorly understood. A huaxian capsule (HXC) is a herbal preparation with putative effects for SS treatment. Here, we aimed to investigate the metabolic changes in SS rats by performing metabolic profiling and biomarker analysis. The phenotypic response was assessed by UPLC/MS combined with chemometrics. As a result, 12 potential metabolite biomarkers were identified and involved in multiple dysregulated metabolic pathways, such as glycerophospholipid metabolism, steroid hormone biosynthesis, and disrupted sphingolipid metabolism, etc. Then, we performed microRNA analysis to reveal that the HXC ameliorates the dysregulated expression profiling of SS. We identified 56 miRNAs that were differentially expressed in the HXC group compared with the model group, of which 20 were down-regulated and 36 were up-regulated. This study showed that microRNA and metabolic profiling is a valuable approach for exploring metabolism responses to herbal drugs, and can improve our understanding of the molecular basis of the SS treatment.