Ribonuclease attenuates acute intestinal injury induced by intestinal ischemia reperfusion in mice

Int Immunopharmacol. 2020 Jun:83:106430. doi: 10.1016/j.intimp.2020.106430. Epub 2020 Apr 9.

Abstract

Ribonuclease (RNase) reportedly exerts organ-protective effects in several pathological conditions, including ischemia reperfusion (I/R), but whether it can exhibit protective effect on intestinal I/R injury and potential mechanisms remain unknown. The present study was aimed to evaluate the effects of RNase on intestinal I/R injury and explore the underlying mechanisms. Thirty-two wild-type C57BL/6J adult male mice were evenly divided into a sham group, a sham + RNase group, an I/R group and an I/R + RNase group. Intestinal I/R was produced by clamping the superior mesenteric artery for 1 h followed by reperfusion for 2 h. All mice were treated with 3 doses of RNase or the same dosage of normal saline at different points. It was found that intestinal I/R caused significant intestinal injury and an increase in levels of extracellular RNAs (exRNAs). Treatment with RNase significantly reduced the inflammatory cytokine production, inhibited intestinal apoptosis and down-regulated the expression of toll like receptor 3 in intestinal tissues. In conclusion, increased exRNAs may contribute to intestinal I/R injury in adult mice, and RNase treatment during perioperative window is effective for attenuating intestinal I/R injury.

Keywords: Apoptosis; Inflammation; Intestine; Ischemia/reperfusion; RNase.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Apoptosis / drug effects
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Intestinal Diseases / drug therapy*
  • Intestinal Diseases / etiology
  • Intestinal Diseases / metabolism
  • Intestines / blood supply
  • Intestines / drug effects*
  • Intestines / injuries*
  • Intestines / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha / drug effects
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • RNA / metabolism
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*
  • Ribonucleases / pharmacology*
  • Ribonucleases / therapeutic use
  • Survival Rate
  • Toll-Like Receptor 3 / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • NF-kappa B
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • NF-KappaB Inhibitor alpha
  • RNA
  • Ribonucleases