δ、κ阿片受体在舒芬太尼预处理减轻大鼠心肌缺血再灌注损伤中的作用

Role of delta and kappa opioid receptors in sufentanil preconditioning-induced attenuation of myocardial ischemia-reperfusion injury in rats

目的 评价δ、κ阿片受体在舒芬太尼预处理（SPC）减轻大鼠心肌缺血再灌注损伤中的作用.方法 健康雄性SD大鼠40只,2～3月龄,体重250～330 g,采用随机数字表法,将其分为5组（n=8）,假手术组（S组）;缺血再灌注组（I/R组）采用结扎左冠状动脉30 min再灌注120 min的方法制备心肌缺血再灌注损伤模型;SPC组在心肌缺血前静脉输注舒芬太尼3μg/kg,输注5 min,停止5min,重复3次进行预处理;δ受体拮抗剂纳曲引哚＋SPC组（NTD＋ SPC组）和κ受体拮抗剂norbinaltorphimine（nor-BNI）＋ SPC组（BNI＋ SPC组）分别于SPC前10 min和15 min静脉注射纳曲引哚和nor-BNI 5 mg/kg.于再灌注120 min时采集动脉血样,测定血清心肌肌钙蛋白Ⅰ（cTnI）和肌酸激酶同工酶（CK-MB）的浓度.处死大鼠后,取心脏,确定心肌梗死区与缺血危险区体积的比值（IS/AAR值）.结果 与S组比较,I/R组、NTD＋ SPC组和BNI＋ SPC组血清cTnI和CK-MB的浓度升高,SPC组血清CK-MB浓度升高,I/R组IS/AAR值升高（P＜0.05或0.01）;与I/R组比较,SPC组、NTD＋ SPC组和BNI＋SPC组血清cTnI和CK-MB的浓度降低,SPC组和BNI＋ SPC组IS/AAR值降低（P＜0.05或0.01）;与SPC组比较,NTD＋ SPC组和BNI＋ SPC组血清cTnI和CK-MB的浓度和IS/AAR值升高（P＜0.05或0.01）.结论 δ、κ阿片受体均介导了SPC减轻大鼠心肌缺血再灌注损伤.

Objective To evaluate the role of delta and kappa opioid receptors in sufentanil preconditioning （SPC）-induced attenuation of myocardial ischemia-reperfusion （I/R） injury in rats.Methods Forty adult male Sprague-Dawley rats,aged 2-3 months,weighing 250-330 g,were randomly divided into 5 groups （n =8 each） using a random number table：sham operation group （group S）,group I/R,group SPC,δ receptor antagonist naltrindole ＋ SPC group （NTD ＋ SPC group）,and κ receptor antagonist nor-binaltorphimine （nor-BNI） ＋ SPC group （BNI ＋ SPC group）.Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.In group SPC,5 min infusion of sufentanil 3μg/kg was repeated 3 times at 5 min interval before myocardial ischemia.In NTD ＋ SPC group,naltrindole 5 mg/kg was intravenously injected,at 10 before SPC.In BNI ＋ SPC group,nor-BNI 5 mg/kg was injected intravenously at 15 min before SPC.Arterial blood samples were collected at 120 min of reperfusion for measurement of the serum cardiac troponin I （cTnI） and creatine kinase isoenzyme-MB （CK-MB） concentrations.The rats were then sacrificed and hearts removed for determination of myocardial infarct size （IS） and area at risk （AAR）.IS/AAR ratio was calculated.Results Compared with S group,the serum cTnI and CK-MB concentrations were significantly increased in I/R,NTD ＋ SPC and BNI ＋ SPC groups,and the serum CK-MB concentrations were increased in SPC group,and IS/AAR ratio was increased in I/R group （P 〈 0.05 or 0.01）.The serum cTnI and CK-MB concentrations were significantly lower in SPC,NTD ＋ SPC and BNI ＋ SPC groups and IS/AAR ratio was lower in SPC and BNI ＋ SPC groups than in I/R group,and higher in NTD ＋ SPC and BNI ＋ SPC groups than in SPC group （P 〈 0.05 or 0.01）.Conclusion Both κ and δ opioid receptors mediate SPC-induced attenuation of myocardial I/R injury in rats.