Effect of oxycodone preconditioning on mitochondrion-dependent apoptosis in liver cells during intestinal ischemia-reperfusion in rats

Abstract

Objective To evaluate the effect of oxycodone preconditioning on mitochondrion-dependent apoptosis in liver cells during intestinal ischemia-reperfusion (I/R) in rats. Methods Fifty-four healthy male Sprague-Dawley rats, weighing 200-300 g, were divided into 9 groups (n=6 each) using a random number table: sham operation group (group S), I/R group, oxycodone preconditioning group (group OP), μ receptor blocker CTOP group (group CTOP), δ receptor blocker naltrindole (NTD) group (group NTD), κ receptor blocker nor-binaltorphimne (BNI) group (group BNI), CTOP plus oxycodone preconditioning group (group CTOP+ OP), NTD plus oxycodone preconditioning group (group NTD+ OP), and BNI plus oxycodone preconditioning group (group BNI+ OP). The model of intestinal I/R was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion.Oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia in OP, COTP+ OP, NTD+ OP and BNI+ OP groups.COTP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+ OP and NTD+ OP groups, respectively.BNI 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+ OP.CTOP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 10 min prior to ischemia in CTOP and NTD groups, respectively.BNI 5 mg/kg was injected intravenously at 15 min prior to ischemia in group BNI.The superior mesenteric artery was only exposed but not occluded in group S. The rats were sacrificed at 2 h of reperfusion, and livers were removed for determination of apoptosis in liver cells (using TUNEL) and expression of Bcl-2 and caspase-3 in liver tissues (by immunohistochemistry). The apoptosis index (AI) was calculated. Results Compared with group S, AI was significantly increased, the expression of Bcl-2 was down-regulated and the expression of caspase-3 was up-regulated in the other eight groups (P<0.05). Compared with group I/R, AI was significantly decreased, the expression of Bcl-2 was up-regulated, and the expression of caspase-3 was down-regulated in group OP (P<0.05). Compared with group OP, AI was significantly increased, Bcl-2 expression was down-regulated, and caspase-3 expression was up-regulated in COTP+ OP, NTD+ OP and BNI+ OP groups (P<0.05). Conclusion The mechanism by which oxycodone preconditioning activates μ, δ and κ receptors and reduces intestinal I/R injury may be related to inhibiting mitochondrion-dependent apoptosis in rats. Key words: Oxycodone; Reperfusion injury; Intestines; Hepatocytes; Apoptosis; Mitochondria