The Role Of PPARγ/NF-κB Signaling Pathway In The Reduction Of Intestinal Ischemia-Reperfusion Injury In Mice By Sodium Butyrate

Objective: To evaluate the role of peroxidase proliferator-activated receptor γ（PPARγ）/NF-kB signaling pathway in the reduction of intestinal ischemia-reperfusion injury by sodium butyrate preconditioning in mice.Methods: 32 SPF-grade healthy adult male C57BL/6J mice,7～9 weeks old,weighing 20～25g,were divided into 4 groups（n=8）by random number table method:Sham operation group（Sham group）,Intestinal ischemia-reperfusion group（II/R group）,Sodium butyrate ischemic preconditioning group（NaB group）and Sodium butyrate ischemic preconditioning+PPARg inhibitor GW9662 group（NaB+GW9662group）.The mouse model of intestinal ischemia-reperfusion injury was prepared by clamping the superior mesenteric artery root for 45 minutes and then followed by for 2hours.NaB+GW9662 group received intraperitoneal injection of GW9662 2 mg/kg 1hour before ischemia,the remaining groups were given equal volume of DMSO;NaB group and NaB+GW9662 group received intraperitoneal injection of sodium butyrate500 mg/kg 30 minutes before ischemia.Blood samples were collected by cardiac puncture at 2 hours after reperfusion,and then the mice were sacrificed,the intestinal tissue samples were obtained at a distance of 5 cm from the distal ileum.The intestinal mucosal was observed after HE stained under a light microscope,and the damage degree was assessed by Chiu’s score;the levels of diamine oxidase（DAO）,interleukins-6（IL-6）and tumor necrosis factor-α（TNF-α）in serum and small intestinal tissue were detected by ELISA;Western blot was used to detect the levels of PPARgand NF-kB p65 in small intestine.Results: Compared with the Sham group,the Chiu’s score in the II/R group increased,the levels of DAO,TNF-α and IL-6 in serum and small intestinal tissue increased,the expression of PPARg in small intestinal tissue was down-regulated,and the expression of NF-kB p65 in small intestinal tissue was up-regulated（P<0.05）.Compared with the II/R group,the Chiu’s score,DAO,TNF-α and IL-6 levels in serum and small intestinal tissue of the NaB group were decreased,the expression of PPARgin small intestinal tissue was up-regulated,and the expression of NF-kB p65 in small intestinal tissue was down-regulated（P<0.05）;compared with the NaB group,the GW9662 group Chiu’s score,DAO,TNF-α,IL-6 levels in the serum and small intestinal tissue increased,the expression of PPARg in small intestinal tissue was down-regulated,and the expression of NF-kB p65 in small intestinal tissue was up-regulated（P<0.05）.Conclusion: The mechanism of sodium butyrate pretreatment to reduce intestinal ischemia-reperfusion injury may be related to activation of PPARg and reduction of NF-kB p65 protein expression,and inhibit inflammatory cytokine release.