Effect of sufentanil preconditioning on acute lung injury induced by intestinal ischemia-reperfusion in rats and the role of opioid receptors

Abstract

Objective To evaluate the effect of sufentanil preconditioning on acute lung injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of opioid receptors.Methods Forty-eight male Wistar rats weighing 200-250 g were randomly divided into 6 groups ( n =8 each):sham operation group (group S) ; I/R group; sufentanil preconditioning group (group SPC) ; COTP (μ receptor antagonist) + SPC group; NTD (δ receptor antagonist) + SPC group and nor-BNI (κ receptor antagonist) + SPC group.Intestinal I/R was produced by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in groups I/R,SPC,COTP +SPC,NTD + SPC and nor-BNI + SPC.Sufentanil 10 μg/kg was injected intravenously at 10 min before ischemia in groups SPC,COTP + SPC,NTD + SPC and nor-BNI + SPC.COTP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 10 min before sufentanil injection in groups COTP + SPC and NTD + SPC respectively,while nor-BNI 5 mg/kg was injected intravenously at 15 min before sufentanil administration in group nor-BNI + SPC.The animals were sacrificed at 2 h of reperfusion,the intestinal tissue was removed for microscopic examination and intestinal damage was assessed and scored according to Chiu.Left lung tissue was also removed for microscopic examination (1 =normal,4 =severely injured).The apoptosis in lung cells was detected using TUNEL and apoptosis index (AI) was calculated.The expression of Bcl-2 and Bax proteins in lung tissues was detected using immuno-histochemistry and Bcl-2/Bax ratio was calculated.Results Compared with group S,Chiu's score,lung injury score and AI were significantly increased,expression of Bcl-2 and Bax proteins was up-regulated,Bcl-2/Bax ratio was significantly decreased in the other groups ( P ＜ 0.01 ).Compared with group I/R,Chiu' s score,lung injury score and AI were significantly decreased,Bcl-2 protein expression was up-regulated,Bax protein expression was downregulated,and Bcl-2/Bax ratio was significantly increased in group SPC (P ＜ 0.01 ).Compared with group SPC,Chiu's score,lung injury score and AI were significantly increased,Bcl-2 protein expression was down-regulated,Bax protein expression was up-regulated,and Bcl-2/Bax ratio was significantly decreased in groups COTP + SPC,NTD + SPC and nor-BNI + SPC ( P ＜ 0.01 ).Conclusion Sufentanil preconditioning can attenuate lung injury induced by intestinal I/R by activation of opioid receptors in rats. Key words: Sufentanil; Ischemic preconditioning; Reperfusion injury; Intestines; Respiratory distress syndrome, adult; Receptors, opioid