Related Experiment Video
Updated: Jul 9, 2026
Rodent Model of Intestinal Ischemia-Reperfusion Injury via Occlusion of the Superior Mesenteric Artery
Published on: October 20, 2023
Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion in rats
Sébastien Gibot1, Frédéric Massin, Corentine Alauzet
1Groupe Choc, Contrat AVENIR INSERM, U684, Faculté de Médecine, Nancy Université, Nancy, France. s.gibot@chu-nancy.fr
Objectives:
The triggering receptor expressed on myeloid cells (TREM)-1, a receptor expressed on the surface of neutrophils and monocytes/macrophages, synergizes with the Toll-like receptors in amplifying the inflammatory response mediated by microbial components. Because the pathogenesis of ischemia-reperfusion-induced gastrointestinal tissue injury and multiple organ failure implies leukocyte activation and bacterial translocation, we hypothesized that the TREM-1 pathway modulation would prove beneficial in this setting.
Design:
Animal study.
Setting:
Research laboratory.
Subjects:
Adult male Wistar rats (250-300 g).
Interventions:
Rats were subjected to intestinal ischemia-reperfusion induced by occlusion of the superior mesenteric artery during 60 mins and reperfused for 180 mins. At the time of reperfusion, animals were administered with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal saline). Plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and soluble TREM-1 were measured by enzyme-linked immunosorbent assay. Hepatic activation of the transcriptional factor nuclear factor-kappaB was assessed by electrophoretic mobility shift assay. Hepatic oxidant-antioxidant balance was estimated by measurement of lipid peroxidation and catalase activity. Ileal mucosal permeability was estimated by fluorescein dextran-4 clearance and bacterial translocation by mesenteric lymph nodes culture.
Measurements And Main Results:
Ischemia-reperfusion was associated with cardiovascular collapse, lactic acidosis, and systemic and hepatic inflammatory response that were partly prevented by LP17 administration. Liver lipid peroxidation and catalase depletion were attenuated by LP17. Ischemia-reperfusion induced a marked increase in ileal mucosal permeability and an associated bacterial translocation that was also prevented by TREM-1 modulation. LP17 delayed mortality.
Conclusions:
The modulation of the TREM-1 pathway by the means of a synthetic peptide may be useful during acute mesenteric ischemia.
Insights
Modulating the TREM-1 pathway with LP17 peptide reduced inflammation and bacterial translocation in a rat model of mesenteric ischemia-reperfusion injury. This TREM-1 inhibition delayed mortality, suggesting therapeutic potential.
Area of Science:
- Immunology
- Gastroenterology
- Surgical Research
Background:
- The triggering receptor expressed on myeloid cells (TREM)-1 amplifies inflammatory responses, playing a role in ischemia-reperfusion injury.
- Leukocyte activation and bacterial translocation are key in gastrointestinal injury and multiple organ failure following ischemia-reperfusion.
Purpose of the Study:
- To investigate the therapeutic potential of modulating the TREM-1 pathway in ischemia-reperfusion-induced gastrointestinal injury.
- To test the hypothesis that TREM-1 pathway inhibition would be beneficial in this setting.
Main Methods:
- Adult male Wistar rats underwent intestinal ischemia-reperfusion.
- Animals were treated with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or vehicle.
- Assessed inflammatory markers (TNF-α, IL-6), oxidative stress, ileal permeability, bacterial translocation, and mortality.
Main Results:
- LP17 partially prevented cardiovascular collapse, lactic acidosis, and systemic/hepatic inflammation.
- LP17 attenuated liver lipid peroxidation and catalase depletion.
- TREM-1 modulation prevented increased ileal permeability and bacterial translocation, and delayed mortality.
Conclusions:
- Modulation of the TREM-1 pathway using a synthetic peptide (LP17) shows promise for treating acute mesenteric ischemia.
- Targeting TREM-1 may offer a novel therapeutic strategy for ischemia-reperfusion injury.
