The Effect Of Selective Opioid Receptor Antagonists On Acute Myocardial Ischemia-reperfusion Injury In Rats

ObjectiveNearly two decades in acute myocardial infarction (AMI) , thrombolysis timely or primary coronary intervention (PCI) generally use to clinic, death rate obviously decrease . However , acute recanalization resulted in reperfusion injury , which made the function of ischemic myocardium be restrained even necrosis , which influent the quality of human life even prognosis . At present , some anima experiments observed ischemia-reperfusion (I-R) injury may be concerned with intracellular calcium overload , oxygen free radical(OFR) and mediators of inflammation . Therefore , how to prevent and cure reperfusion injury have become a hot point that clinical doctors concern about . Recently , it was confirmed that morphine pretreatment could product the effect of the protective to ischemic myocardium through stimulation opiate receptor , but the mechanism of heart protective of morphine function have not been determine . There are three type opiate receptor ; mu (u),delta (δ),kappa (κ) in rodents heart tissue , but onlyδandκ-opiate receptor exist in adult rats heart.the animal model of acute myocardium ischemia-reperfusion (AMIR) injury was established in rats , to test the hypothesis that morphine induce cardioprotection was mediated through stimulation of delta(δ) or kappa (κ)-opiate receptor subtypes in rats , and explore the mechanism of protective effect of morphine on myocardium. MethodsExperiment-1: Healthy female or male Spargue-dawley rats (n=50) were randomly divided into 5 groups(n=10): group A (Ischemia/reperfusion group), group B (morphine preconditioning group ), group C (morphine and Nor-BNI {nor-Binaltorphimine dihydrochloride, a selectiveκ-opiate receptor antagonist}group), group D (morphine and NTI {Naltrindole hydrochloride, a selective 8 -opiate receptor antagonist}group), group E (normal control group). The left anterior descending branch (LAD) of rats coronary artery was tied and untied in group A,group B,group C,group D 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), routine method was used to detect creatine kinase (CK-MB) in serum, The myocardial infarct size were determination by 2,3,5-triphenytelteazolum chloride (TTC). The myocardial cell were observed by transmission electron microscope (TEM).Experiment-2: Group C and group D were divided into group C₁,C₂,C₃ ;D₁,D₂,D₃ (n=5). By turns the ratio of the number of molecules of Nor-BNI or NTI to morphine was 1 : 1,2 : 1,3 : 1. Accorded with the same process to detect ET-1,CK-MB and the myocardial infarct size.Results1. in AMI at 10min : In group A,group B,group C,and group D, Plasma ET-1,CK-MB increased significantly than those group E (P <0.01) , which no difference among in group A,group B,group C,and group D (P >0.05) . in MIR at 4.5h : In group B and group D, Plasma ET-1, CK-MB decreased markedly compared with in group A and group C (p<0.01) , whereas no definite change were observed between group B and group D (P >0.05) , group A and group C too (P >0.05) . Compare the difference of plasma ET-1,CK-MB in MIR at 4.5h and in AMI at 10min: group B compared with group A and group C , Plasma ET-1, CK-MB have significant difference (P <0.01) , however, there have not difference between group B and group D (P>0.05) .2.The infarct size was smaller in group B than those in group A and group C (p<0.01), whereas no definite change were observed between group B and group D (P >0.05) , group A and group C (P>0.05) .3.The ultrastructure injury of myocardial cell such as mitochondria swelling ,cristae rupture ,vacuole denaturation were observed in group A and group C, but the injury in group B and group D were alleviated significantly.4.There were in direct proportion to NTI dose in group D , which decreased plasma ET-1,CK-MB and reduced myocardial infarct size.ConclusionThe study has shown that morphine may be product protective effect on ischemic-reperfusion in rats myocardium by exciting a selectiveκ-opiate receptor , which made plasma ET-1,CK-MB decreased and myocardial infarct size reduced , which significant positive correlation of drug dose.