Effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion in rats

Abstract

Objective To evaluate the effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion(I/R)in rats. Methods Thirty-six healthy male Sprague-Dawley rats, aged 4-5 months, weighing 200-250 g, were randomly divided into 4 groups(n=9 each)using a random number table: sham operation group(group S), intestinal I/R group(group I/R), low-dose dexmedetomidine group(group LD), and high-dose dexmedetomidine group(group HD). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 1 h followed by 2 h reperfusion in anesthetized rats.Dexmedetomidine 2.5 and 5.0 μg·kg-1·h-1 were infused via the caudal vein for 1 h starting from 1 h before ischemia in LD and HD groups, respectively.The rats were sacrificed at 2 h of reperfusion, and the gastric mucosa was obtained for examination of the pathological changes(with light microscope)and for determination of the expression of serine/threonine kinase(Akt), phosphorylated Akt(p-Akt), activated caspase-3 and caspase-3(by Western blot). The ratio of p-Akt to Akt(p-Akt/Akt)was calculated to reflect the phosphorylation of Akt.The ratio of activated caspase-3 to caspase-3(activated caspase-3/caspase-3)was calculated to reflect the activation of caspase-3. Results Compared with group S, the expression of Akt was significantly up-regulated, the expression of p-Akt was significantly down-regulated, the phosphorylation of Akt was significantly decreased, and the activation of caspase-3 was significantly increased in group I/R, and the expression of p-Akt was significantly up-regulated, and the phosphorylation of Akt and activation of caspase-3 were significantly increased in LD and HD groups(P<0.05). Compared with group I/R, the expression of Akt was significantly down-regulated, the expression of p-Akt was significantly up-regulated, the phosphorylation of Akt was significantly increased, and the activation of caspase-3 was significantly decreased in LD and HD groups(P<0.05). The degree of gastric mucosal injury was significantly lower in LD and HD groups than in group I/R, and there was no significant difference in the degree of gastric mucosal injury between group LD and group HD. Conclusion Dexmedetomidine can attenuate gastric mucosal injury induced by intestinal I/R, and the mechanism may be related to activation of PI3K/Akt signaling pathways and inhibition of cell apoptosis in rats. Key words: Dexmedetomidine; Reperfusion injury; Intestine; Gastric mucosa