吗啡对急性心肌梗死再灌注损伤保护效应的实验研究

Protective effect and mechanism of morphine on acute myocardial ischemia/reperfusion injury in rats

目的 通过测定急性心肌梗死再灌注损伤模型大鼠的血浆降钙素基因相关肽 (CGRP)、内皮素(ET 1)浓度及心肌梗死面积的变化 ,探索吗啡对急性心肌损伤的保护机制。方法 将 4 0只 SD大鼠随机分为单纯缺血再灌注模型组、吗啡预处理组、吗啡 +纳洛酮组和手术对照组 ,每组各 10只。采用戊巴比妥钠(40 m g/ kg)腹腔注射麻醉大鼠 ,采用穿线结扎左冠状动脉前降支制备大鼠心肌缺血再灌注模型。用放射免疫法测定血浆 CGRP和 ET 1浓度 ,同时测定血清中肌酸磷酸激酶同工酶 (CK MB)含量 ;用氯化三苯四唑(TTC)法染色和数码照相计算机图像分析系统计算心肌梗死面积。结果 大鼠左冠状动脉前降支结扎 10 m in时血浆 ET 1和 CGRP浓度较手术对照组显著增高 (P均 <0 .0 1) ;再灌注 4 .5 h时吗啡预处理组血浆 ET 1及 CK MB浓度较结扎 10 m in时显著降低 ,心肌梗死面积也显著缩小 (P均 <0 .0 1) ;而血浆 CGRP浓度则显著增高 (P<0 .0 1) ;吗啡预处理组以上变化较吗啡 +纳洛酮组差异有统计学意义 (P均 <0 .0 1)。结论 吗啡预处理可通过显著降低 ET 1而增加 CGRP血浆浓度、缩小心肌梗死面积 ,对急性心肌梗死后再灌注心肌产生保护效应。

Objective To explore the protective effect of morphine and its mechanism on acute myocardial ischemia/reperfusion(AMIR) injury in rats, by the method of detecting calcitonin generelated peptide(CGRP) and endothelin1(ET1) levels, as well as myocardial infarct size. Methods Forty SD rats were randomly divided into four groups: ischemia/reperfusion group( n =10 ), morphine preconditioning group( n =10),morphine and naloxone hydrochloride group( n =10), and normal controls( n =10). The animal model of AMIR was established in rats. The left anterior descending branch(LAD) of rat coronary was tied and untied. Animals were then sacrificed and hearts were harvested to determine myocardial infarct size by 2 , 3, 5triphenyteltrazolium chloride(TTC). Radioimmunoassay was used to detect CGRP and ET1 levels in plasma, and routine method was used to measure creatine kinase isoenzyme(CKMB) in serum . Results Plasma ET1 and CGRP levels were increased significantly than that in normal controls in acute myocardial infarction(AMI) at 10 minutes of LAD tied(all P <0 01). Plasma ET1 and CKMB levels in morphine preconditioning group in AMIR at 4 5 hours of reperfusion were decreased significantly as compared with that in the same group in AMI at 10 minutes, and myocardial infarct size decreased significantly (all P <0 01), while, plasma CGRP levels were markedly increased. Significant differences in those parameters were found between morphine preconditioning group and morphine combined with naloxone hydrochloride group (all P <0 01). Conclusion Intravenous morphine has protective effects on AMI by increased plasma CGRP level, decreased plasma ET1 level, and reduced myocardial infarct size.