The Signal Passway Of KOR In Post-resuscitation Myocardial Dysfunction In Rats

ObjectiveTo investigate the κ opioid receptor (kappa opioid receptor, KOR) signal passway modulating myocardial dysfunction after cardioc arrest cardiopulmonary resuscitaion (CPR) in rats.To investigate the mechanism of kappa opioid receptor in protecting postresuscitation myocardial dysfunction.To privide a potential method to improve postresuscitation myocardial dysfunction.MethodA total of 120 rats were randomized into three groups, control group(C group), kappa opioid receptor agonist group(U group), κ opioid receptor inhibitor group(G group). Each group was divided into five subgroups according to 5 sections (lh,2h,6h,12h,24h). All rats were oral intubated, a polyethylene catheter was advanced through the left femoral artery and into the descending aorta for measurement of aortic pressure and sampling of arerial blood. Conventional lead Ⅱ ECG was continuously monitored. Body temperature was measured and maintained at 37±0.5℃. Asphyxia-induced CA Was performed by turning-off the ventilator and blocking the endotracheal tube. Chest compressions and mechanical ventilations were started after 6 minutes of CA.The baseline arterial blood gas was measured; hemodynamic data of heart rate,MAP,BP, DBP were continuously recorded. The rat hearts were harvested at lh,2h,4h,6h,12h and 24h after resuscitation in each group and 0.5h after animal preparation in Control group; 8 for each time-point in each group.The expressions of KOR, GRK3, phos-KOR, phos-AKT, phose-ERK protein in myocardium were detected by methods of Western blot.The expressions of KOR and GRK3 mRNA in myocardium were detected by methods of RT-PCR.ResultThe baseline of body weight,anesthesia dose,oxygen pressure, arterial carbon dioxide pressure, arterial bicarbonate, lactic acid, hemodynamics data included heart rate,blood heart rate, blood pressure,etc. were no statistic significant among 3 groups.2. At the 90 minutes of post-resuscitation, the heart rate of U group was higher than the C group (p<0.05), at the time points of 60mins,90mins,120mins after post-resuscitation, G group systolic, diastolic, and mean blood pressure higher than the C group (p<0.01).3. The mRNA expression of KOR in U group was significantly higher compared with C group after resuscitation.The protein expression of GRK3 in U group was significantly higher compared with C group after resuscitation and G group was significantly decreased compared with C group.The mRNA expression of GRK3 in G group was significantly decreased compared with C group at the 6hours and 24 hours after resuscitation. The protein expression of phose-KOR in U group was significantly higher compared with C group and G group was significantly decreased than C group after one hours after resuscitation. The protein expression of phose-ERK in U group was significantly higher compared with C group and G group was significantly decreased than C group after resuscitation at the each time point. The protein expression of phose-AKT in U group was significantly higher compared with C group and G group was significantly decreased than C group after two hours after resuscitation. The variation tendency of the ERK1/2 is the same with phos-KOR.Conclusion1 κ opioid receptor which is in myocardial cells is activated in the SD-rat model of cardiopulmonary arrest resuscitation caused by asphyxia.2 GRK3 is related with the KOR after ischemia and reperfusion injur.3 In the process of reperfusion, ERK1/2 and PI3K/AKT pathways activated by the κ-opioid receptor activation, when the κ opioid receptor suppressed, the pathways will be inhibition.4 Kappa opioid receptor protects heart which suffers ischemia-reperfusion may be through the ERK1/2 and PI3KAKT pathways.