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Objective To compare the effects of oxycodone and morphine on myocardial ischemiareperfusion (I/R) injury in rats.Methods Forty-eight SPF healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-300 g,were randomized into 4 groups (n =12 each) using a random number table:sham operation group (S group),myocardial I/R injury group (I/R group),morphine group (M group) and oxycodone group (O group).Myocardial I/R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min of reperfusion.In group S,the anterior descending branch of the left coronary artery was only exposed but not ligated.In M and O groups,morphine 1.5 mg/kg and oxvcodone 0.5 mg/kg were injected,respectively,via the internal jugular vein at 5 min before ischemia.At the end of reperfusion,arterial blood samples were collected via cardiac puncture for determination of the serum creatine kinase-MB (CK-MB) and cardiac troponin Ⅰ (cTnI) concentrations.Myocardial infarct size was measured by 2,3,5-triphenyhetrazolium chloride staining.Apoptosis in cardiomyocytes was determined by TUNEL,and apoptosis index (AI) was calculated.Results Compared with S group,serum CK-MB and cTnI concentrations and AI were significantly increased,and myocardial infarct size was enlarged in I/R,M and O groups (P＜0.05).Compared with I/R group,serum CK-MB and cTnI concentrations and AI were significantly decreased,and myocardial infarct size was decreased in M and O groups (P＜0.05).Serum CK-MB and eTnI concentrations and AI were significantly lower,and myocardial infarct size was smaller in O group than in M group (P＜0.05).Conclusion Oxycodone produces better efficacy than morphine in reducing myocardial I/R injury in rats.
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Objective To evaluate the effect of oxycodone pretreatment on autophagy during renal ischemia-reperfusion (I/R) in rats.Methods Thirty-six SPF healthy adult male Wistar rats,aged 6-9 weeks,weighing 180-220 g,were divided into 3 groups (n=12 each) using a random number table:sham operation group (Sham group),I/R group and oxycodone pretreatment group (Oxy group).The left renal pedicles were clamped with atraumatic microclips for 45 min followed by reperfusion to establish the model of renal I/R injury in I/R and Oxy groups.Oxycodone 0.5 mg/kg was injected via the caudal vein at 15 min before ischemia in group Oxy,and the equal volume of normal saline was given instead in I/R and Sham groups.At 24 h of reperfusion,blood samples were collected from hearts for measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations.The animals were then sacrificed and left renal tissues were obtained for examination of pathological changes (with a light microscope) and for determination of Bcl-2 and Beclin-1 expression (by immunohistochemistry).Results Compared with Sham group,the concentrations of serum Cr and BUN were significantly increased,and the expression of Bcl-2 and Beclin-1 in renal tissues was up-regulated at 24 h of reperfusion in I/R and Oxy groups (P<0.05).Compared with I/R group,the concentrations of serum Cr and BUN were significantly decreased,the expression of Bcl-2 in renal tissues was up-regulated,and the expression of Beclin-1 in renal tissues was down-regulated at 24 h of reperfusion (P<0.05),and the pathological changes were significantly attenuated in Oxy group.Conclusion Oxycodone pretreatment inhibits autophagy through up-regulating the expression of Bcl-2 and down-regulating the expression of Beclin-1,thus attenuating renal I/R injury in rats.
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Objective To investigate the effects of sinomenine on hind limb ischemia?reperfusion ( I∕R) injury and expression of Bcl?2 and Bax in skeletal muscle cells of rats. Methods Fifty?four healthy adult male Wistar rats, aged 6-8 weeks, weighing 180-220 g, were divided into 3 groups ( n=18 each) using a random number table: sham operation group ( group S) , group I∕R and sinomenine group ( group SIN) . The rats were subjected to 4 h of ischemia on the proximal part of the right hind limb using elastic rubber bands followed by reperfusion in I∕R and SIN groups. Sinomenine 60 mg∕kg was injected intraperito?neally at 30 min before reperfusion in group SIN, and the equal volume of normal saline was given instead of sinomenine at 30 min before reperfusion in S and I∕R groups. Immediately after onset of reperfusion and at 4 and 24 h of reperfusion, blood samples were collected from the cardiac apex to measure the concentra?tions of serum lactate dehydrogenase ( LDH) and creatine kinase ( CK) . The animals were sacrificed imme?diately after blood sampling, and the gastrocnemius specimens of the hind limb were immediately removed for determination of the wet to dry weight ratio ( W∕D ratio) and expression of Bcl?2 and Bax in gastrocnemi?us cells ( by immunohistochemistry) and for examination of the pathological changes after haematoxylin and eosin staining. The Bcl?2∕Bax ratio was calculated. Results Compared with group S, the gastrocnemius W∕D ratio and concentrations of serum LDH and CK were significantly increased, the expression of Bcl?2 was significantly down?regulated, the expression of Bax was significantly up?regulated, and the Bcl?2∕Bax ratio was significantly decreased in I∕R and SIN groups ( P<0?05) . Compared with group I∕R, the gastroc?nemius W∕D ratio and concentrations of serum LDH and CK were significantly decreased, the expression of Bcl?2 was significantly up?regulated, the expression of Bax was significantly down?regulated, and the Bcl?2∕Bax ratio was significantly increased in group SIN ( P<0?05) . The pathological changes of the gastrocne?mius were significantly attenuated in group SIN as compared with group I∕R. Conclusion Sinomenine can attenuate hind limb I∕R injury, and the mechanism may be related to maintenance of the balance between Bcl?2 and Bax and to inhibition of apoptosis in skeletal muscle cells of rats.
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Objective To evaluate the effect of oxycodone postconditioning on myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty pathogen-free healthy adult male Sprague-Dawley rats,weighing 200-300 g,were randomly divided into 4 groups (n =10 each) using a random number table:sham operation group (group S),myocardial I/R group (group Ⅰ),oxycodone postconditioning group (group O),and selective protein kinase C inhibitor chelerythrine group (group CH).Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery,followed by 120 min reperfusion.In group S,the left anterior descending branch of the coronary artery was only exposed but not ligated.In group CH,chelerythrine 5 mg/kg was injected intravenously and slowly via the jugular vein before ligation which was performed immediately after administration.In O and CH groups,oxycodone 0.5 mg/kg was injected intravenously and slowly via the jugular vein at 2 min before reperfusion.Arterial blood samples were taken at 120 min of reperfusion to detect the levels of cardiac troponin Ⅰ (cTnI) and creatine kinase-MB (CK-MB) in serum.The hearts were removed after the animals were sacrificed to measure the myocardial infarct size by TTC staining.Results Compared with group S,the levels of cTnI and CK-MB in serum and myocardial infarct size were significantly increased in Ⅰ,O and CH groups (P＜0.05).Compared with group Ⅰ,the levels of cTnI and CK-MB in serum and myocardial infarct size were significantly decreased in O and CH groups (P＜0.05).Compared with group O,the levels of cTnI and CK-MB in serum and myocardial infarct size were significantly increased in group CH (P＜0.05).Conclusion Oxycodone postconditioning can mitigate myocardial I/R injury in rats,and the mechanism is partially related to activation of protein kinase C signaling pathway.