The Research Of Delta、Kappa Opioid Receptors In Myocardial Protection Of Sufentanil Preconditioning

Objective To discuss on the roles of delta、kappa opioid receptors in the cardioprotective effects of sufentanil preconditioning and the mechanism of myocardial protectionby sufentanil preconditioning through observation of the Cx43.Methods Seventy adult male Sprague-Dawley rats, aged2-3months, weighing250-330g, were randomly divided into5groups(n=14):control group(C),ischemia-reperfusiongroup (I/R), sufentanil preconditioning group (SPC):sufentanil,3μg/kg, was administered viaa venous pump thrice before ligating the left anterior descending coronary; eachadministration lasted5min with a5min interval in-between. Naltrindole+sufentanilpreconditioning group(NTD+SPC) and nor-Binaltorphimine+sufentanil preconditioninggroup(BNI+SPC): Naltrindole(δ Opioid receptor antagonist) and nor-Binaltorphimine(κopioid receptor antagonist),5mg/kg, were administered intravenously10min and15minrespectively before SPC. Heart rate (HR),and Mean arterial pressure (MAP) were recordedbefore conditioning treatment(T0), immediately prior to the ischemia(T1),30min afterischemia(T2),30min after reperfusion(T3) and120min after reperfusion(T4), systolic bloodpressure and heart rate (RPP) were caculated. The electrocardiogram was recorded and scoredfor arrhythmia. Arterial blood samples were collected at the end of reperfusion formeasurement of the plasma cTnI and CK-MB concentrations. The rats were then sacrificedand the heart tissue was adopted for the later determination. Even’s blue-TTC staining wasused to detect the myocardial infarct size. An immunohistochemical staining was used to detect the expression of Cx43protein in myocardial cells and RT-PCR was used to detect theamount of Cx43mRNA.Results1. The difference of HR in each group were not statistically significant(P>0.05);Compare with C group, MAP of T4, RPP of T24, in I/R group were decreased（P<0.05）;Compared with I/R group, MAP and RPP of T1in SPC group were decreased, RPP of T2inNTD+SPC group was increased（P<0.05）; Compared with SPC group, MAP and RPP of T1in NTD+SPC group and BNI+SPC group were increased, RPP of T2in NTD+SPC group wasincreased（P<0.05）; Compared with T0, MAP and RPP of T2-4in I/R group were decreased,MAP and RPP of T1-4in SPC group were decreased, MAP of T2-4and RPP of T4inBNI+SPC group were decreased（P<0.05）; Compared with T1, MAP of T2and RPP of T2-4in I/R group were decreased（P<0.05）2. Compare with C group, the plasma cTn-I andCK-MB concentrations and the arrhythmia scores in I/R group, NTD+SPC group andBNI+SPC group were increased（P<0.05）, the value of Cx43OD and the expression of Cx43mRNA in the other four groups were decreased（P<0.05）; Compared with I/R group, theinfarct areas in SPC group, BNI+SPC group were decreased（P<0.01）, the arrhythmia scoresin SPC group, NTD+SPC group were decreased（P<0.05）,the plasma cTn-I and CK-MBconcentrations in SPC group, NTD+SPC group and BNI+SPC group were decreased（P<0.05）, the value of Cx43OD and the expression of Cx43mRNA in SPC group wereincreased（P<0.05）; Compared with SPC group, the infarct areas, the plasma cTn-I andCK-MB concentrations were increased and the value of Cx43OD and the expression of Cx43mRNA were decreased in NTD+SPC group, BNI+SPC group were increased（P<0.05）, thearrhythmia scores in BNI+SPC group were increased（P<0.05）.Conclusions1. Delta and kappa opioid receptors participated in sufentanilpreconditioning-induced attenuation of myocardial I/R injury, delta opioid receptor mainlyproduced anti-infract area effects, Kappa opioid receptor mainly produced anti-arrhythmiceffects.2. The myocardial protection of sufentanil pretconditionging may regulated the expression of Cx43through excited delta and kappa opioid receptors.