δ受体在芬太尼后处理和肢体远隔缺血后处理对大鼠心肌缺血／再灌注损伤保护效应中作用的实验研究  

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

作　　者：许亚超[1] 薛富善[2] 袁玉静[2] 王强[2] 廖旭[2] 程怡[2] 李瑞萍[2] 刘建华[2] 王天龙[1] 

机构地区：[1]首都医科大学附属宣武医院麻醉科,北京100053 [2]中国医学科学院北京协和医学院整形外科医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2012年第3期151-156,163,共7页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金资助项目（30972836）

摘　　要：目的探讨8受体在芬太尼后处理和肢体远隔缺血后处理对大鼠心肌缺血／再灌注损伤（ischernia／reperfusioninjury，I／RI）保护作用机制中的地位。方法通过结扎冠状动脉左前降支（left anterior descending coronary artery，LAD）造成局部心肌缺血30min后开放血流再灌注180min建立心肌I／RI模型。将72只大鼠按随机数字表法随机平均分为4组（每组18只），分别在结扎LAD15min时给予芬太尼（30μg／kg）、远隔缺咀后处理、联合应用芬太尼和远隔缺血后处理或生理盐水（对照）。在结扎LAD前5min，将每组大鼠平均分成A和B两个亚组，分别静脉注入生理盐水和8受体拮抗剂Naltrindole hydrochloride（NTD）。再灌注180min时，测定血浆肌酸激酶MB同工酶（creatine kinase isoenzymeMB，CK．MB）和血清心肌肌钙蛋白I（cardiactroponinI，cTnI）活性，采用伊文氏蓝和氯化三苯基四氮唑染色法测定心肌梗死面积（infarctsize，IS％）值。结果C-A亚组、F-A亚组、R．A亚组、F-R-A亚组、c—B亚组、F-B亚组、R-B亚组和F-R—B亚组的IS％值分别是（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）％。芬太尼后处理和肢体远隔缺血后处理可显著降低心肌缺血／冉灌注后的IS％值以及CK-MB和cTnI活性，联合应用芬太尼后处理和肢体远隔缺血后处理可获得显著增强的心肌保护效果。NTD可显著削弱肢体远隔缺血后处理的心肌保护作用，但对芬太尼后处理的心肌保护作用无影响。预先应用NTD能够消除联合应用芬太尼后处理和肢体远隔缺血后处理在降低IS％值方面的协同作用。结论8受体参与肢体远隔缺血后处理的心肌保护作用，但未参与芬太尼后处理的心肌保护作用。6受体对联合应用芬太尼后处理和肢体远隔缺血后处理在降低心肌梗死面�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-triphenyhetrazolium 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.

关 键 词：心肌缺血/再灌注损伤 心肌保护 远隔缺血后处理 药物后处理 阿片受体 

分 类 号：R614[医药卫生—麻醉学]