大鼠再灌注期问美沙酮急性治疗通过δ-阿片受体减少心肌梗死面积  

作　　者：任三姐(译) 周仁龙 杭燕南(校) Eric R, Gross PhD Anna K Hsu Garrett J. Gross 

机构地区：[1]Department of Anesthesiology, Stanford University, Stanford, California [2]Department of Pharmacology and Toxi-cology, Medical College of Wisconsin, Milwaukee, Wisconsin

出　　处：《麻醉与镇痛》2013年第1期1-8,共8页Anesthesia & Analgesia

摘　　要：背景美沙酮是一种阿片激动剂，常用于治疗急慢性疼痛。本文探讨美沙酮是否与吗啡一样剂量依赖地减少心肌梗死面积（infarctsize，IS）及其机制是否由δ-阿片受体介导。此外还检测心肌IS的减少是否随美沙酮给药时间或诱发缺血持续时间而发生变化。方法做好手术准备后，将雄性SD大鼠分为3组。第1组又分为缺血前30分钟接受美沙酮（0．03-3mg／kg）、吗啡（0．03-3mg／kg）和水（安慰剂）的3个亚组。第1组的部分动物在给予美沙酮（0．3mg／kg）、吗啡（0．3mg／kg）或安慰剂前也注射8．阿片拮抗剂纳曲吲哚（5mg／kg）。第2组分为再灌注前5分钟或再灌注后10秒接受美沙酮（0．3mg／kg）治疗亚组。这2组中的动物通过左前降支冠状动脉夹闭造成心肌缺血30分钟，然后再灌注2小时。第3组动物通过夹闭左前降支冠状动脉造成缺血45分钟，于再灌注前5分钟接受安慰剂，美沙酮（0．3mg／kg），或吗啡（0．3mg／kg），然后再灌注2小时。用三苯基氯化四唑染色心肌组织评价心肌IS，以危险区（areaatrisk，AAR）所占百分比表示（均数±标准误）。结果缺血前给予美沙酮或吗啡可减少心肌IS。最大效应出现于0．3mg／kg剂量组（美沙酮，46％±1％，P〈0．001和吗啡，47％±1％，P〈0．001，与安慰剂的61％±1％相比）。纳曲吲哚（5mg／kg）阻断美沙酮（0．3mg／kg）和吗啡（0．3mg／kg）诱导的心肌保护作用（与美沙酮相比，纳曲吲哚＋美沙酮，58％±1％，P〈0．001，与吗啡相比，纳曲吲哚＋吗啡，58％±1％，P〈0．001）。再灌注前5分钟给予美沙酮（0．3mg／kg）时减少心肌IS（与安慰剂相比，46％±1％，P〈0．001，），但再灌注后10秒时给予美沙酮则无这种效应（与安慰剂相比，60％±1％，P=0．675）。安慰剂组与45分钟缺血组（64％±1％）和30分钟缺血组（60％±1％，尸=0．069�BACKGROUND： Methadone is an opioid agonist often given to manage acute and chronic pain. We sought to determine whether methadone compared with morphine dose dependently reduces myocardial infarct size （IS） and whether the mechanism is δ-opioid receptor mediated. Furthermore, we examined whether myocardial IS reduction varies with the timing of methadone administration or duration of induced ischemia. METHODS： After surgical instrumentation, we divided male Sprague-Dawley rats into 3 sets. The first set was divided into groups, which received methadone （0. 03 - 3 mg/kg）, morphine （0. 03 -3 mg/kg）, or water （placebo） 30 min before ischemia. Some animals of the first set also received the δ-opioid antagonist naltrindole （5 mg/kg） before methadone （0.3 mg/kg）, morphine （0.3 mg/kg）, or placebo administration. The second set of animals was divided into groups that received methadone （0.3 mg/kg） 5 min before reperfusion or 10 s after reperfusion. These 2 sets of animals were subjected to 30 min of myocardial ischemia by left anterior descending coronary artery ocdusion and then 2 h of reperfusion. The third set of animals received placebo, methadone （0. 3 mg/kg）, or morphine （0. 3 mg/kg） 5 min before reperfusion and were subjected to 45 rain of ischemia by left anterior descending coronary artery occlusion with 2 h of reperfusion. Myocardial IS was assessed by staining myocardial tissue with triphenyltetrazolium chloride and expressed as a percentage of the area at risk （mean ± sere）. RESULTS： Methadone or morphine administered before ischemia reduced myocardial IS. The greatest effect was achieved at a dose of 0.3 mg/kg （methadone, 46% ± 1%, P 〈 0. 001 and morphine, 47% 1%, P 〈 0. 001 versus placebo, 61% ± 1%, respectively）. Naltrindole （5 mg/kg） blocked methadone-induced （0. 3 mg/ kg） and morphine-induced （0.3 mg/kg） cardioprotection （naltrindole ＋ methadone, 58% ± 1%, P 〈 0.001 versusmethadone; and naltrindole morphine, 58 ±1%, P 〈

关 键 词：心肌梗死面积 Δ-阿片受体 再灌注期 急性治疗 美沙酮 SD大鼠 心肌缺血 纳曲吲哚 

分 类 号：R542.22[医药卫生—心血管疾病]