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Updated: Mar 30, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine
Eszter Tuboly1, Mitsuru Futakuchi2, Gabriella Varga1
1Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
Abstract:
Acute mesenteric ischemia (AMI) is caused by considerable intestinal injury, which is associated with intestinal ischemia followed by reperfusion. To elucidate the mechanisms of ischemia/reperfusion injuries, a C5a inhibitory peptide termed AcPepA was used to examine the role of C5a anaphylatoxin, induction of inflammatory cells, and cell proliferation of the intestinal epithelial cells in an experimental AMI model. In this rat model, the superior mesenteric artery was occluded and subsequently reperfused (Induce-I/R). Other groups were treated with AcPepA before ischemia or reperfusion. Induce-I/R induced injuries in the intestine and AcPepA significantly decreased the proportion of severely injured villi. Induce-I/R induced secondary receptor for C5a-positive polymorphonuclear leukocytes in the vessels and CD204-positive macrophages near the injured site; this was correlated with hypoxia-induced factor 1-alpha-positive cells. Induction of these inflammatory cells was attenuated by AcPepA. In addition, AcPepA increased proliferation of epithelial cells in the villi, possibly preventing further damage. Therefore, Induce-I/R activates C5a followed by the accumulation of polymorphonuclear leukocyte and hypoxia-induced factor 1-alpha-producing macrophages, leading to villus injury. AcPepA, a C5a inhibitory peptide, blocks the deleterious effects of C5a, indicating it has a therapeutic effect on the inflammatory consequences of experimental AMI.
Insights
A C5a inhibitory peptide, AcPepA, reduced intestinal injury in an experimental acute mesenteric ischemia (AMI) model. AcPepA also decreased inflammatory cell accumulation and enhanced epithelial cell proliferation, suggesting therapeutic potential for AMI.
Area of Science:
- Gastroenterology
- Immunology
- Inflammation Research
Background:
- Acute mesenteric ischemia (AMI) involves intestinal injury due to ischemia and reperfusion.
- The role of C5a anaphylatoxin in AMI-induced inflammation and epithelial damage is not fully understood.
Purpose of the Study:
- To investigate the therapeutic effects of a C5a inhibitory peptide, AcPepA, in an experimental AMI model.
- To elucidate the mechanisms of ischemia/reperfusion injury, focusing on inflammatory cell infiltration and epithelial cell proliferation.
Main Methods:
- An experimental AMI model was established in rats by occluding and reperfusing the superior mesenteric artery.
- Rats were treated with AcPepA before ischemia or reperfusion.
- Intestinal injury, inflammatory cell markers (PMNs, macrophages), and epithelial cell proliferation were assessed.
Main Results:
- Induction of ischemia/reperfusion (I/R) caused significant intestinal injury.
- AcPepA treatment significantly reduced the severity of villus injury.
- AcPepA attenuated the induction of C5a receptor-positive polymorphonuclear leukocytes and CD204-positive macrophages, which correlated with hypoxia-induced factor 1-alpha.
- AcPepA promoted intestinal epithelial cell proliferation.
Conclusions:
- Ischemia/reperfusion in AMI activates C5a, leading to inflammatory cell accumulation and villus injury.
- AcPepA effectively blocks the detrimental effects of C5a, demonstrating therapeutic potential for mitigating inflammation in experimental AMI.
