Dynamic metabolomic analysis of intestinal ischemia-reperfusion injury in rats

IUBMB Life. 2020 May;72(5):1001-1011. doi: 10.1002/iub.2238. Epub 2020 Jan 30.

Abstract

Intestinal ischemia-reperfusion injury (IIR) is a life-threatening abdominal emergency. Compared to traditional steady-state works, we profiled the blood of rats over 72 hr (15 time points) and examined dynamic changes in molecular pathways during IIR. Using a series of methods designed for dynamic datasets analysis (batch effects corrections, metabolomics data reduction, and different features selection), we identified 39 significant different metabolites and discovered the trends of these molecules. Four main patterns were uncovered by a longitudinal pattern recognition method. Furthermore, pathway networks were explored to uncover the possible mechanisms of IIR. We found that IIR is a complex physiological process involved in multiple pathways, such as biosynthesis of amino acids, 2-oxocarboxylic acid metabolism, arginine-related metabolism, and glutathione metabolism. Among which, metabolites related with phenylalanine tyrosine and tryptophan metabolism reached a peak during the early stage of reperfusion, while molecules in biosynthesis of unsaturated fatty acids metabolism declined. Our work provides a feasible scheme to understand dynamic molecule variation and will provide new explications about the effect of intestinal ischemia reperfusion from a dynamic perspective.

Keywords: biosynthesis of unsaturated fatty acids metabolism; dynamic metabolomics; intestinal ischemia-reperfusion injury; pathway networks; phenylalanine tyrosine and tryptophan metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood
  • Animals
  • Chemokine CCL3 / blood
  • Disease Models, Animal
  • Fatty Acids / blood
  • Gas Chromatography-Mass Spectrometry
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / blood
  • Male
  • Mesenteric Arteries / surgery
  • Metabolic Networks and Pathways / physiology*
  • Metabolomics / methods*
  • Oxidative Stress
  • Phospholipids / blood
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood*
  • Reperfusion Injury / pathology
  • Surgical Instruments
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Amino Acids
  • Chemokine CCL3
  • Fatty Acids
  • IL1B protein, rat
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Phospholipids
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma