Effect of oxycodone on intestinal ischemia-reperfusion injury in rats and the role of autophagy / 中华麻醉学杂志

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 LC3 Ⅱ expression to LC3 Ⅰ expression (LC3 Ⅱ / Ⅰ) was calculated.Results Compared with group S,the Chiu's score,levels of serum FITC-dextran,TNF-α and IL-1β and LC3 Ⅱ/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 I/R,the Chiu's score and levels of serum FITC-dextran,TNF-α and IL-1β were significantly decreased,LC3 Ⅱ / Ⅰ ratio was increased,and the expression of occludin and Beclin-1 was up-regulated in group O (P＜0.05),and no significant change was found in the parameters mentioned above in group O+ 3-MA (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,LC3 Ⅱ / 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.