Sevoflurane Protects against Intestinal Ischemia-Reperfusion Injury by Activating Peroxisome Proliferator-Activated Receptor Gamma/Nuclear Factor-κB Pathway in Rats

Intestinal ischemia/reperfusion (I/R) injury is a clinical challenge with high morbidity and mortality, whereas the effective therapeutic strategy is limited. Inflammatory reaction plays important roles in I/R-induced intestinal damage and multi-organ dysfunction syndrome. Peroxisome proliferator-activated receptor gamma (PPARγ) has been identified as an endogenous anti-inflammatory regulator by inhibiting nuclear factor-κB (NF-κB) activation. Our previous research has shown that the pretreatment with inhaled anesthetic sevoflurane protects intestinal I/R injury. However, whether the protection induced by sevoflurane is mediated by inhibiting intestinal inflammatory reaction via activation of PPARγ/NF-κB pathway is underdetermined. In this study, we investigated the effects of sevoflurane on intestinal inflammatory reaction during intestinal I/R and the role of PPARγ/NF-κB pathway.

Rat model of intestinal I/R was used in this study. The superior mesenteric artery was clamped for 60 min followed by 120-min reperfusion. Sevoflurane at 0.5 minimum alveolar concentration was inhaled for 30 min before ischemic insult. GW9662, a specific PPARγ antagonist, was injected intraperitoneally before sevoflurane inhalation.

Intestinal I/R caused severe intestinal mucosa histopathological injury evaluated by Chiu's scoring, induced epithelial cell apoptosis evaluated by terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling and activation of caspase-3, upregulated serum MOD levels, reduced protein expression of Bcl-2 and PPARγ, increased protein expression of NF-κB P65 and proinflammatory cytokine tumor necrosis factor-α and interleukin-6 in the intestine. Sevoflurane preconditioning significantly ameliorated these changes induced by intestinal I/R. However, GW9662 partly blocked the protective effects induced by sevoflurane.

Our results suggest sevoflurane-induced protection against intestinal I/R injury is partly mediated by inhibiting intestinal inflammatory reaction via activation of PPARγ/NF-κB pathway.