PLOS One · Nov 4, 2026
Treadmill prehabilitation attenuates jejunal inflammation and enhances cytoprotective protein expression in murine gut ischemia–reperfusion
By Higashizono K, Takahashi K, Fukatsu K et al.
Introduction: Whether preoperative exercise protects the intestine itself is unclear. We hypothesized that treadmill prehabilitation acts on the intestine as ischemic preconditioning, and examined intestinal injury and cytokine responses after gut ischemia–reperfusion (I/R) and jejunal cytoprotective protein expression before ischemia. Methods: Two experiments were conducted in male C57BL/6J mice. In Experiment 1, mice were randomly allocated to a sedentary or an exercise group; exercised mice completed 1 week of acclimation and 3 weeks of treadmill running. One day after the final session, the superior mesenteric artery was occluded for 45 min. Jejunal and ileal cytokines were measured in 24 mice, and mucosal injury was graded by the Chiu classification in 22 mice, at 3 or 6 h after reperfusion. In Experiment 2, separate cohorts completed 0 (SED, n = 5), 1 (EX1, n = 5), 2 (EX2, n = 4) or 3 (EX3, n = 5) weeks of running, and jejunal HSP70, Bcl-2 and p62 were quantified by western blotting without I/R. Results: Injury scores were lower in exercised mice (jejunum at 3 h, 1.10 ± 0.22 vs 2.60 ± 0.50; main effect of exercise, P = 0.0025 [jejunum] and P < 0.0001 [ileum]). Jejunal IL-12 at 3 h (adjusted P = 0.042) and IL-6 at 6 h (adjusted P = 0.015) were lower in exercised mice, whereas in the ileum a main effect of exercise was found for IL-12 (P = 0.037) without adjusted between-group differences. HSP70/β-actin was higher in EX1–EX3, and p62/β-actin lower in EX2–EX3, than in SED (Bonferroni-corrected threshold, P < 0.017). Training duration was associated positively with HSP70/β-actin (R² = 0.55, P = 0.0003) and Bcl-2/β-actin (R² = 0.31, P = 0.014) and negatively with p62/β-actin (R² = 0.31, P = 0.014); group comparisons for Bcl-2 were not significant. Conclusion: Treadmill prehabilitation was accompanied by less mucosal injury and a smaller early jejunal inflammatory response after gut I/R, and the jejunum before ischemia differed in cytoprotective and autophagy-related protein expression according to training duration, consistent with ischemic preconditioning of the intestine.