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Updated: Mar 12, 2026
Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy
Published on: September 27, 2024
Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?
Olivér Rosero1, Péter Ónody1, Tibor Kovács1
11st Department of Surgery, Semmelweis University, Budapest, Hungary.
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.
Insights
Postconditioning effectively reduced intestinal ischemia-reperfusion injury by decreasing toll-like-receptor-4 expression and improving the inflammatory response. This method offers a promising strategy for mitigating organ damage after mesenteric arterial occlusion.
Area of Science:
- Gastroenterology
- Surgical Research
- Immunology
Background:
- Ischemia-reperfusion injury (IRI) of the intestine is a significant clinical concern following mesenteric artery occlusion.
- Toll-like receptor 4 (TLR4) plays a critical role in the inflammatory cascade and organ damage associated with IRI.
Purpose of the Study:
- To investigate the therapeutic potential of postconditioning in reducing intestinal IRI.
- To examine the effect of postconditioning on the mucosal expression of toll-like receptor 4 (TLR4) in a rat model.
Main Methods:
- Male Wistar rats underwent superior mesenteric artery occlusion for 60 minutes followed by 6 hours of reperfusion.
- Postconditioning was applied using alternating cycles of reperfusion and reocclusion.
- Assessment included intestinal histopathology, immunohistochemistry for caspase-3, antioxidant status, and protein levels of HMGB1 and TLR4, as well as inflammatory cytokines (IL-6, TNF-α).
Main Results:
- Postconditioning significantly ameliorated histologic damage in the intestine compared to the IRI group.
- Reduced expression of caspase-3, TLR4 mRNA, HMGB1, IL-6, and TNF-α was observed in postconditioned rats.
- An improved antioxidant status of the intestinal mucosa was noted in the postconditioned group.
Conclusions:
- Postconditioning is an effective strategy for mitigating small intestinal ischemia-reperfusion injury in rats.
- The protective effects of postconditioning may be mediated by the downregulation of toll-like receptor 4 (TLR4) expression and a more favorable inflammatory profile.
