Glutamine protects intestine against ischemia-reperfusion injury by alleviating endoplasmic reticulum stress induced apoptosis in rats

Acta Cir Bras. 2020 Mar 9;35(1):e202000104. doi: 10.1590/s0102-865020200010000004. eCollection 2020.

Abstract

Purpose: Glutamine, as an essential part of enteral nutrition and parenteral nutrition agent, has been widely recognized to be a kind of important intestinal mucosa protectant in clinical practice and experimental research. However, the mechanisms of its protective effects are still not fully understand. Consequently, this study aimed to explore the potential mechanism of glutamine on ischemia-reperfusion (I/R) injury induced endoplasmic reticulum (ER) stress in intestine.

Methods: An experimental model of intestinal I/R in rats was established by 1 hour occlusion of the superior mesenteric artery followed by 3 hours of reperfusion. Morphologic changes of intestinal mucosa, apoptosis of epithelial cells, and expression of intestinal Grp78, Gadd153, Caspase-12, ATF4, PERK phosphorylation (P-PERK) and elF2αphosphorylation(P-elF2α) were determined.

Results: After I/R, the apoptotic index of intestinal mucosa epithelial cells observably increased with notable necrosis of intestinal mucosa, and the expressions of Grp78, Gadd153, Caspase-12, ATF4, P-PERK and P-elF2αall were increased. However, treatment with glutamine could significantly relieve intestinal I/R injury and apoptosis index. Moreover, glutamine could clearly up-regulate the expression of Grp78, restrain P-PERK and P-elF2α, and reduce ATF4, Gadd153 and Caspase-12 expressions.

Conclusion: Glutamine may be involved in alleviating ER stress induced intestinal mucosa cells apoptosis.

MeSH terms

  • Activating Transcription Factor 4 / drug effects
  • Animals
  • Apoptosis / drug effects*
  • Caspase 12 / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Glutamine / pharmacology*
  • Heat-Shock Proteins / drug effects
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / ultrastructure
  • Male
  • Mesenteric Artery, Superior / injuries
  • Models, Animal
  • Protective Agents / pharmacology*
  • RNA, Messenger / drug effects
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Transcription Factor CHOP / drug effects
  • eIF-2 Kinase / drug effects

Substances

  • Atf4 protein, rat
  • Ddit3 protein, rat
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Protective Agents
  • RNA, Messenger
  • Glutamine
  • Activating Transcription Factor 4
  • Transcription Factor CHOP
  • PERK kinase
  • eIF-2 Kinase
  • Caspase 12