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High-throughput lipidomics enables discovery of the mode of action of huaxian capsule impacting the metabolism of sepsis

机译:高通量脂质组学可以发现花县胶囊影响败血症代谢的作用方式

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Severe sepsis (SS) is a major cause of mortality and morbidity in the intensive care unit and requires rapid diagnosis and treatment. Lipids are key regulators of cellular function; hence, in this study, we hypothesized that lipid levels could be altered in patients suffering from SS. Lipidomics is the comprehensive analysis of molecular lipid species. In this study, we used an untargeted lipidomics approach coupled with multivariate data analysis and bioinformatics analysis to profile the metabolic changes of sepsis induced by cecal ligation and puncture (CLP) in rats and investigated the treatment effects of huaxian capsule (HXC), a herbal medicine with putative effects in SS treatment. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and pattern recognition methods were employed to evaluate the metabolic phenotypic changes. Differentially expressed lipids have been further analyzed using the ingenuity pathway analysis (IPA) software, a tool that discloses functional pathways associated with lipids of interest. As a result, ten lipids involved in multiple metabolic pathways, such as in glycerophospholipid metabolism, ether lipid metabolism, purine metabolism, and tryptophan metabolism representing characteristic phenotypes, were identified by pathway analysis. HXC administration can reverse lipid phenotype changes induced by CLP; this indicates that the effectiveness of HXC as an SS treatment depends on modulation of the lipid metabolic changes. Our study shows that lipidomics is a valuable method that can provide additional insight into the underlying mechanisms of HXC in the SS treatment.
机译:严重脓毒症(SS)是重症监护病房死亡率和发病率的主要原因,需要快速诊断和治疗。脂质是细胞功能的关键调节因子。因此,在这项研究中,我们假设患有SS的患者的脂质水平可能会改变。脂质组学是对分子脂质种类的综合分析。在这项研究中,我们使用非靶向脂质组学方法,结合多变量数据分析和生物信息学分析,分析了盲肠结扎和穿刺(CLP)诱导的大鼠脓毒症的代谢变化,并研究了草药化纤胶囊(HXC)的治疗效果在SS治疗中具有公认疗效的药物。采用超高效液相色谱/四极杆飞行时间质谱(UPLC-Q-TOF-MS)和模式识别方法评估代谢表型的变化。差异表达的脂质已使用独创性途径分析(IPA)软件进行了进一步分析,该工具可公开与目标脂质相关的功能性途径。结果,通过途径分析鉴定了十个参与多种代谢途径的脂质,例如参与甘油磷脂代谢,醚脂质代谢,嘌呤代谢和色氨酸代谢的代表特征表型。 HXC给药可以逆转CLP诱导的脂质表型改变;这表明HXC作为SS疗法的有效性取决于脂质代谢变化的调节。我们的研究表明,脂质组学是一种有价值的方法,可以为SS治疗中HXC的潜在机制提供更多见解。

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