Role of PI3K/Akt signaling pathway in propofol-induced reduction of intestinal ischemia-reperfusion injury in rats

Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in propofol-induced reduction of intestinal ischemia-reperfusion (I/R) injury in rats. Methods Thirty-two healthy male Sprague-Dawley rats, aged 2-3 months, weighing 225-275 g, were divided into 4 groups (n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), propofol group (P group), and PI3K inhibitor wortmannin plus propofol group (W+ P group). Intestinal ischemia was induced by occluding the superior mesenteric artery for 45 min followed by 2 h of reperfusion to establish the model of intestinal I/R injury.Propofol was intravenously infused at a rate of 20 mg·kg-1·h-1 starting from the onset of reperfusion until the end of reperfusion in group P. Wortmannin 15 μg/kg was intravenously injected at 25 min before reperfusion, and propofol was intravenously infused at a rate of 20 mg·kg-1·h-1 starting from the onset of reperfusion until the end of reperfusion in group W+ P.Rats were sacrificed at 2 h of reperfusion, and small intestinal tissues were obtained for microscopic examination of pathologic changes of intestinal mucosa and for determination of wet/dry weight ratio (W/D ratio), malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method), superoxide dismutase (SOD) activity (using xanthine oxidase method), myeloperoxidase (MPO) activity (by MPO assay), and phosphorylated Akt (p-Akt) expression (by Western blot). Intestinal damage was assessed and scored according to Chiu. Results Compared with group Sham, Chiu′s score, W/D ratio, MDA content and MPO activity were significantly increased, the SOD activity was decreased, and p-Akt expression was down-regulated in group I/R (P<0.05). Compared with group I/R, Chiu′s score, W/D ratio, MDA content and MPO activity were significantly decreased, the SOD activity was increased, and p-Akt expression was up-regulated in group P (P<0.05). Compared with group P, Chiu′s score, W/D ratio, MDA content and MPO activity were significantly increased, the SOD activity was decreased, and p-Akt expression was down-regulated in group W+ P (P<0.05). Conclusion The mechanism by which propofol reduces intestrnal I/R injury is related to activating PI3K/Akt signaling pathway and inhibiting inflammatory and oxidative stress responses in rats. Key words: Propofol; Reperfusion injury; Intestines; Phosphatidylinositol 3-kinase; Protein kinases