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采用 UHPLC-Q-Orbitrap-HRMS 技术的脓毒症大鼠肺组织代谢组学方法及血必净注射液的干预作用

Metabolomics approach in lung tissue of septic rats and the interventional effects of Xuebijing injection using UHPLC-Q-Orbitrap-HRMS.

机构信息

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan Province,, PR China.

College of Food Science and Engineering, Dalian Ocean University, No. 52 Heishijiao Street, Shahekou District, Dalian, Liaoning Province, PR China.

出版信息

J Biochem. 2018 Dec 1;164(6):427-435. doi: 10.1093/jb/mvy070.

Abstract

Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction. Metabolomic profiling in bio-fluid or tissue is vital for elucidating the pathogenesis of sepsis and evaluating therapeutic effects of medication. In this study, an untargeted metabolomics approach was applied to study the metabolic changes in lung tissue of septic rats induced by cecal ligation and puncture (CLP) and investigate the treatment effects of Xubijing injection (XBJ). Metabolomics analyses were performed on ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) together with multivariate statistical analysis. A total of 26 differential metabolites between CLP and sham-operated group were identified. The altered metabolic pathways included energy metabolism, amino metabolism, lipid metabolism, fatty acid metabolism and hormone metabolism. Among the 26-varied metabolites, 15 were significantly regulated after XBJ treatment. The metabolic pathway network of sepsis was drawn to interpret the pathological feature of lung damage caused by sepsis and the underlying regulating mechanism of XBJ on the molecular levels. Our findings display that LC-MS-based metabolomics is a useful tool for uncovering the underlying molecular mechanism of sepsis, and XBJ may exert therapeutic effect by regulating multiple metabolic pathways.

摘要

脓毒症是宿主对感染的失调反应,可导致危及生命的器官功能障碍。在生物液体或组织中进行代谢组学分析对于阐明脓毒症的发病机制和评估药物治疗效果至关重要。在这项研究中,应用非靶向代谢组学方法研究了盲肠结扎和穿刺(CLP)诱导的脓毒症大鼠肺组织的代谢变化,并探讨了血必净注射液(XBJ)的治疗效果。采用超高效液相色谱-Q Exactive 杂交四极杆轨道阱高分辨率精确质量质谱(UHPLC-Q-Orbitrap-HRMS)结合多变量统计分析进行代谢组学分析。在 CLP 组和假手术组之间共鉴定出 26 个差异代谢物。改变的代谢途径包括能量代谢、氨基酸代谢、脂质代谢、脂肪酸代谢和激素代谢。在 26 种变化的代谢物中,15 种在 XBJ 治疗后显著调节。绘制了脓毒症的代谢途径网络,以解释脓毒症引起的肺损伤的病理特征以及 XBJ 在分子水平上对其的调节机制。我们的研究结果表明,基于 LC-MS 的代谢组学是揭示脓毒症潜在分子机制的有用工具,XBJ 可能通过调节多种代谢途径发挥治疗作用。

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