Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?

Surgery. 2017 Apr;161(4):1004-1015. doi: 10.1016/j.surg.2016.09.031. Epub 2016 Nov 11.

Abstract

Background: Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4.

Methods: Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured.

Results: Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group.

Conclusion: Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biopsy, Needle
  • Blotting, Western
  • Disease Models, Animal
  • Immunohistochemistry
  • Intestinal Mucosa / blood supply
  • Ischemic Postconditioning / methods*
  • Ischemic Preconditioning / adverse effects
  • Ischemic Preconditioning / methods
  • Male
  • Mesenteric Ischemia / pathology*
  • Mesenteric Ischemia / therapy*
  • Microscopy, Confocal
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / prevention & control*
  • Toll-Like Receptor 4 / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers
  • Reactive Oxygen Species
  • Toll-Like Receptor 4