Effect of oxycodone on intestinal ischemia-reperfusion injury in rats and the role of autophagy

Abstract

Objective To evaluate the effect of oxycodone on intestinal ischemia-reperfusion injury in rats and the role of autophagy. Methods Twenty-four healthy adult male Sprague-Dawley rats, aged 6-9 weeks, weighing 180-220 g, were divided into 4 groups(n=6 each)using a random number table method: sham group(group S), intestinal I/R group(group I/R), oxycodone group(group O)and oxycodone plus autophagy inhibitor 3-methyladenine(3-MA)group(group O+ 3-MA). Intestinal I/R was induced via clamping the superior mesenteric artery for 1 h, followed by 2-h reperfusion in all the groups except for group S. Oxycodone 0.5 mg/kg was injected via caudal vein at 15 min before ischemia in group O and group O+ 3-MA.3-MA 30 mg/kg was intraperitoneally injected at 10 min before ischemia in group O+ 3-MA.Rats were gavaged with fluorescein-isothiocyanate-conjugated dextran(FITC-dextran)immediately before ischemia.Blood samples were collected from the cardiac apex at 2 h of reperfusion to detect the level of serum FITC-dextran.Blood samples were collected from the cardiac apex at 2 h of reperfusion to measure the concentrations of tumor necrosis factor-alpha(TNF-α)and interleukin-1beta(IL-1β)in serum by enzyme-linked immunosorbent assay.Small intestinal tissues were obtained at 2 h of reperfusion for examination of the pathological changes and for determination of the expression of occludin, Beclin-1 and microtubule-associated protein 1 light chain 3(LC3)(by Western blot). Intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression(LC3Ⅱ/Ⅰ)was calculated. Results Compared with group S, the Chiu′s score, levels of serum FITC-dextran, TNF-α and IL-1β and LC3Ⅱ/Ⅰ ratio were significantly increased, the expression of Beclin-1 was up-regulated, and the expression of occludin was down-regulated in group I/R(P 0.05). Compared with group O, the Chiu′s score and levels of serum FITC-dextran, TNF-α and IL-1β were significantly increased, LC3Ⅱ/Ⅰ ratio was decreased, and the expression of occludin and Beclin-1 was down-regulated in group O+ 3-MA(P<0.05). Conclusion Oxycodone can ameliorate intestinal I/R injury, and the mechanism may be related to enhancing autophagy in intestinal tissues of rats. Key words: Oxycodone; Reperfusion injury; Intestine; Autophagy