不同剂量δ受体拮抗剂对急性心肌梗死大鼠内皮素、心肌酶及梗死面积的影响

摘要

目的 采用吗啡及不同剂量δ受体拮抗剂纳曲吲哚盐酸盐(NTI)组,观察其对急性心肌缺血-再灌注大鼠内皮素、心肌酶及心肌梗死面积的影响,以说明δ受体拮抗剂可增强吗啡对大鼠急性心肌缺血-再灌注心肌的保护作用,且与剂量成正相关.方法 健康SD大鼠雌雄不拘共25只,每组5只,随机分成单纯缺血再灌注组、吗啡组、吗啡+小剂量NTI组、吗啡+中剂量NTI组、吗啡+大剂量NTI组,建立大鼠心肌缺血-再灌注模型.分别于缺血前10 min及再灌注4.5 h采血及采取组织标本,采用放射免疫法测定血浆内皮素-1,免疫抑制分析法测定心肌酶,用氯化三苯基四氮唑染色测定心肌梗死面积,数码照相图像分析系统计算心肌梗死面积.结果 吗啡+大剂量NTI组较其他实验组可显著降低大鼠血浆内皮素-1、心肌酶(P＜0.01)及缩小心肌梗死面积(P＜0.01),而吗啡组与小剂量及中剂量NTI组两两之间差异无统计学意义.结论 δ受体拮抗剂可通过降低血浆内皮素、心肌酶及缩小心肌梗死面积而增强吗啡对大鼠急性心肌缺血-再灌注心肌的保护作用.%Objective To observe the effects of morphine and different drug dose of selective delta-opioid receptor antagonist on endothelin, MB isoenzyme creatine kinase (CK-MB) and myocardial infarct size in rats with acute myocardial infarction to describe S receptor antagonist's enhancement of morphine to the cardioprotection in rats with acute myocardial ischemic/reperfusion (AMIR) injury. And to explore the positive correlation of this protective effects on myocardium with drug dose. Methods Healthy female or male SD rats (n=25) were randomly divided into 5 groups (n=5): ischemia/reperfusion group, morphine group, morphine and low dose naltrindole hydrochloride and a selective 5-opioid receptor antagonist (NTI) group, morphine and moderate dose NTI group, morphine and large dose NTI group. The left anterior descending branch of the rats coronary artery was tied and untied in all groups to establish the AMIR model in rats. The animals were then sacrificed and hearts were harvested. Radioimmunoassay was used to detect endothelia-1 (ET-1), and routine method was used to detect CK-MB in serum. The myocardial infarct size was determined by 2, 3, 5-triphenytelteazolum chloride. The myocardial cell was observed by transmission electron microscope. Results In morphine and large dose NTI group, plasma ET-1, CK-MB decreased markedly in myocardial ischemic/reperfusion at 4.5 h compared with in ischemia/reperfusion group, morphine group, morphine and low dose NTI group, morphine and moderate dose NTI group (P <0.01), but these data had no marked difference in morphine group, morphine and low dose NTI group, morphine and moderate dose NTI group. Conclusion S receptor antagonist may enhance the cardioprotection of morphine in rats with AMIR injury, which makes plasma ET-1, CK-MB decrease and myocardial infarct size reduce. It has a significant positive correlation with drug dose.