Chuiliang Liu1, Ruiwen Ding2, Wujian Huang3, Liping Miao3, Junhua Li3, Yujuan Li4. 1. Department of Anesthesiology, ChanCheng Center Hospital, Foshan, China. 2. Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China. 3. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 4. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, yujuan_04@hotmail.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: O A Afolabi; T M Akhigbe; R E Akhigbe; B A Alabi; O T Gbolagun; M E Taiwo; O O Fakeye; E O Yusuf Journal: Front Pharmacol Date: 2022-09-23 Impact factor: 5.988