Simvastatin Alleviates Intestinal Ischemia/Reperfusion Injury by Modulating Omi/HtrA2 Signaling Pathways

Transplant Proc. 2019 Oct;51(8):2798-2807. doi: 10.1016/j.transproceed.2019.04.076. Epub 2019 Jul 24.

Abstract

Purpose: The objective of this research was to survey the therapeutic action of simvastatin (Sim) on intestinal ischemia/reperfusion injury (II/RI) by modulating Omi/HtrA2 signaling pathways.

Methods: Sprague Dawley rats were pretreated with 40 mg/kg Sim and then subjected to 1 hour of ischemia and 3 hours of reperfusion. The blood and intestinal tissues were collected, pathologic injury was observed, the contents of serum tumor necrosis factor-α and interleukin-6 (IL-6) were estimated, and superoxide dismutase, methane dicarboxylic aldehyde, and cysteinyl aspartate specific proteinase-3 (caspase-3) levels, as well as the expressions of Omi/HtrA2 and caspase-3, were measured in the intestinal tissues.

Results: Sim preconditioning mitigated the damnification of intestinal tissues by decreasing oxidative stress, inflammatory damage, and apoptosis and downregulating the expression of Omi/HtrA2 compared to the ischemia/reperfusion group, while Sim+Ucf-101 significantly augmented this effect.

Conclusion: These results suggest that Sim may alleviate intestinal ischemia/reperfusion injury by modulating Omi/HtrA2 signaling pathways.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers / analysis
  • Caspase 3 / metabolism
  • High-Temperature Requirement A Serine Peptidase 2 / physiology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Mitochondrial Proteins / metabolism
  • Pyrimidinones
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Signal Transduction / drug effects
  • Simvastatin / pharmacology*
  • Superoxide Dismutase / metabolism
  • Thiones

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Mitochondrial Proteins
  • Pyrimidinones
  • Thiones
  • UCF 101
  • Simvastatin
  • Superoxide Dismutase
  • High-Temperature Requirement A Serine Peptidase 2
  • CASP3 protein, human
  • Caspase 3