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Updated: Mar 12, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Influences of Vagotomy on Gut Ischemia-Reperfusion Injury in Mice
Motonari Ri1, Kazuhiko Fukatsu, Taiki Miyakuni
1*Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan †Department of Surgical Center, The University of Tokyo, Tokyo, Japan ‡Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan §Department of Laboratory of Veterinary Surgery, The University of Tokyo, Tokyo, Japan.
Background:
How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear.
Materials And Methods:
Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured.
Results:
Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group.
Conclusions:
Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.
Insights
Vagotomy significantly worsens survival and increases inflammatory cytokines in the gut after ischemia-reperfusion injury. This study highlights the negative impact of vagotomy on host responses to gut I/R.
Area of Science:
- Gastroenterology
- Surgical Research
- Immunology
Background:
- The impact of vagotomy on host responses to gut ischemia-reperfusion (I/R) remains largely unexplored.
- Gut I/R is a critical condition with significant morbidity and mortality.
Purpose of the Study:
- To investigate how vagotomy influences the host's response to gut ischemia-reperfusion (I/R).
- To assess the effects of vagotomy on survival, cytokine profiles, and intestinal tissue damage following gut I/R.
Main Methods:
- Three experiments were conducted using male Institute of Cancer Research mice.
- Experiment 1 assessed survival in I/R versus vagotomy-I/R groups over 48 hours.
- Experiments 2 and 3 evaluated plasma and tissue cytokine levels (IL-6, MCP-1, IFN-γ, TNF-α) and gut histology at various time points post-reperfusion, including ex vivo tissue culture.
Main Results:
- Vagotomy significantly worsened survival rates in mice subjected to gut I/R compared to controls.
- Vagotomy led to increased levels of pro-inflammatory cytokines, including IL-6 and MCP-1 in plasma and jejunum, and IFN-γ in the jejunum.
- Severe intestinal injury was observed in the vagotomy-I/R group, with correlations between plasma and intestinal cytokine levels.
Conclusions:
- Vagotomy exacerbates the negative outcomes of gut ischemia-reperfusion.
- The combined effect of vagotomy and I/R results in heightened systemic and local inflammation and increased tissue damage.
- These findings suggest that vagotomy may compromise the host's ability to manage gut I/R injury.
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