Roles of δ-opioid receptor in the cardioprotective effects of fentanyl postconditioning and remote ischemic postconditioning against rat myocardial ischemia/reperfusion injury in vivo

The Journal of Clinical Anesthesiology Pub Date : 2012-03-15 DOI:10.3760/CMA.J.ISSN.1673-4378.2012.03.002

Yanling Xu, Tian-Long Wang

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Abstract

Objective To investigate the roles of δ-opioid receptor in the cardioprotective effects by fentanyl postconditioning and limb remote ischemia postconditioning (RIPOC). Methods Myocardial ischemia/reperfusion injury (IRI)model was established by ligation of the left anterior descending coronary artery (LAD) for 30 min and then reperfusion for 180 min.Seventy-two rats were randomly divided into four groups,which received fentanyl (30 μg/kg),RIPOC,combined fentanyl and RIPOC,or saline only (placebo)at 15 min after LAD ligation.Animals of each group were further divided into the subgroup A which received saline only 5 min before LAD ligation and subgroup B which received the δ-opioid antagonist naltrindole (NTD,5 mg/kg).At the end of reperfusion,level of creatine kinase isoenzyme MB (CK-MB) in plasma and serum activity of cardiac troponin I (cTnI)were measured,and infarct size (IS％ value) was determined by 2,3,5 -triphenyltetrazolium chloride staining. Results The IS％values of subgroups C-A,F-A,R-A,F-R-A,C-B,F-B,R-B,and F-R-B were (59.6±3.1),(55.6±2.2),(48.4±1.4),(35.5±1.7),(57.9 ±2.0),(52.2±2.4),(50.3 ± 1.2)％ and (46.9 ±2.8)％,respectively.Both fentanyl postconditioning and RIPOC significantly decreased the IS％ value,CK-MB and cTnI level induced by IRI,and these effects were enhanced as fentanyl postconditioning plus RIPOC.Effect of fentanyl postconditioning but not RIPOC against IRI,was attenuated by NTD.Also,synergistic effect between the fentanyl postconditioning and RIPOC on infarct size sparing disappeared when pretreated with NTD.Conclusions The δ-opioid receptor was involved in the cardioprotection of fentanyl postconditioning,but not in RIPOC,and it plays an important role in the synergistic effect in combination with the fentanyl PPOC and RIPOC. Key words: Myocardial ischemia/reperfusion injury; Cardioprotection; Remote ischemia postconditioning; Pharmacological postconditioning; Opioid receptor

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δ-阿片受体在芬太尼后适应和远端缺血后适应对大鼠心肌缺血/再灌注损伤的保护作用中的作用

目的探讨δ-阿片受体在芬太尼后处理和肢体远端缺血后处理(RIPOC)对心脏保护作用中的作用。方法采用左冠状动脉前降支结扎30 min，再灌注180 min的方法建立心肌缺血再灌注损伤(IRI)模型，将72只大鼠随机分为4组，分别于结扎后15 min给予芬太尼(30 μg/kg)、RIPOC、芬太尼与RIPOC联合用药、单纯生理盐水(安慰剂)。各组动物进一步分为在LAD结扎前5 min给予生理盐水的A组和给予δ-阿片拮抗剂纳曲多(NTD,5 mg/kg)的B组。再灌注结束时，测定血浆肌酸激酶同工酶MB (CK-MB)水平和血清心肌肌钙蛋白I (cTnI)活性，采用2,3,5 -三苯四唑氯化染色法测定梗死面积(IS%值)。结果子组c - a %值,二,r, F-R-A, cb, F-B, R-B,和F-R-B(59.6±3.1),(55.6±2.2),(48.4±1.4),(35.5±1.7),(57.9±2.0),(52.2±2.4),(50.3±1.2)%和(46.9±2.8)%,分别。芬太尼后处理和RIPOC均可显著降低IRI诱导的IS%值、CK-MB和cTnI水平，且芬太尼后处理加RIPOC可增强上述作用。NTD可减弱芬太尼后处理而非RIPOC对IRI的作用。此外，经NTD预处理后，芬太尼后处理和RIPOC对梗死面积保留的协同作用消失。结论δ-阿片受体参与芬太尼后处理的心脏保护作用，而不参与RIPOC，在芬太尼PPOC和RIPOC联合作用中发挥重要的协同作用。关键词:心肌缺血/再灌注损伤;心脏保护;远端缺血后适应;药理后处理;阿片受体

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