Role of PPARγ/NF-κB signaling pathway in sodium butyrate-induced reduction of intestinal ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of peroxidase proliferator-activated receptor γ (PPARγ)/nuclear factor kappa B (NF-κB) signaling pathway in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF-grade healthy adult male C57BL/6J mice, aged 7-9 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (IIR group), sodium butyrate group (NaB group) and PPARγ inhibitor GW9662 group (GW9662 group). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.GW9662 2 mg/kg was intraperitoneally injected at 1 h before ischemia in GW9662 group, and sodium butyrate 500 mg/kg was intraperitoneally injected at 30 min before ischemia in NaB and GW9662 groups.Blood samples were obtained via cardiac puncture at 2 h of reperfusion, and the animals were then sacrificed.The intestinal tissues were removed for determination of diamine oxidase (DAO), tumor necrosis factorα (TNF-α) and interleukins 6 (IL-6) concentrations in serum (by enzyme-linked immunosorbent assay) and the expression of PPAR and NF-κB p65 (by Western blot). The damage to intestinal mucous membrane was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score was significantly increased, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group IIR ( P<0.05). Compared with group IIR, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were decreased, and expression of PPARγ was up-regulated in group NaB, and expression of NF-κB p65 was up-regulated in NaB and GW9662 groups ( P<0.05). Compared with group NaB, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, and expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group GW9662 ( P<0.05). Conclusion:The mechanism by which sodium butyrate reduces intestinal I/R injury may be related to activating PPARγ/NF-κB signaling pathway and inhibiting inflammatory responses in mice.