Effects Of The Spinal Cord Neurons Potassium Channel In Intrathecal Morphine Preconditioning-mediated Cardioprotection Against Myocardial Ischemia-reperfusion Injury In SD Rats And Its Mechanisms

Background and Objectives:Ischemic Heart Disease(IHD)is one of the most common disease,The myocardial ischemia reperfusion injury caused by restore blood flow supply after acute myocardial ischemia can increase the area of myocardial infarction(MI),consequently affect the cardiac function recovery.Previous studies have confirmed that intrathecal morphine preconditioning can activate the spinal cord opioid receptors thus reduce the myocardial ischemia reperfusion injury,and the spinal cord neurons potassium channel is a downstream effector of various opioid receptors.The objectives of this study were to observe the effect of the spinal cord neurons potassium channel in intrathecal morphine preconditioning-mediated cardioprotection against myocardial ischemia reperfusion injury in SD rats,and discuss the potential mechanism Methods:Seventy male adult SD rats,weight 250-350 g,with successful intrathecal catheter placement were selected.A randomized number table was used for dividing all the SD rats into seven groups(n=10):the control group(Sham),ischemia reperfusion injury group(IRI group),IRI+non-selective potassium channel opener nicorandil group(IRI+NICO group),intrathecal morphine preconditioning group(ITMP group),ITMP+non-selective potassium channel blocker glibenclamide group(ITMP+GLI),SHAM+non-selective potassium channel opener nicorandil group(Sham+NICO group),IRI+non-selective potassium blocker glibenclamide group(IRI+GLI).The myocardial ischemia reperfusion injury model was performed by ligating the LAD for 30 min followed by reperfusion for 2 h.Inject 10 ?l solution of 0.9 % NaCl and10 ?l morphine at 3 ?g/kg intrathecally 40 min and 30 min prior to ischemia,respectively,for 5 min intermitted by 5 min pause,3 cycles in total in ITMP group.Infuse 10 ?l: 100 ?g NICO intrathecally 40 min before ischemia in IRI+NICO group.In ITMP+GLI group,perfuse the GLI intrathecally before morphine preconditioning.Record the HR and times of ventricular arrhythmia(PVCs,ventricular tachycardia,ventricular fibrillation)during the 30 min of reperfusion.The rats were sacrificed reperfusion,and the hearts were acquired for TTC staining to calculate the infarct size(IS)and the area at risk(AAR)as well as the ratio of IS/AAR.Preserve the upper segment of the spinal cord,detect the expression of TRPV1 and phosphorylated TRPV1(p-trpv1)protein,NGF and its receptor tyrosine kinase A(TrkA)by Western Blot.Results:Compared with the Sham group,the times of PVCs and VT ?the ratio of IS/AAR of all groups were significantly increased(P < 0.05);compared with the IRI group,the times of PVCs and VT as well as the ratio of IS/AAR were decreased in the IRI+NICO and ITMP groups(P < 0.05);compared with the ITMP group,the times of PVCs and VT as well as the ratio of IS/AAR in the ITMP+GLI group were increased significantly(P < 0.05).Compared with the IRI group,the expression of NGF,TRKA,TRPV1 and p-trpv1 in the IRI+NICO group and the ITMP group were decreased,while the expression of four proteins in ITMP+GLI group was higher compared to ITMP group.Conclusions1.The opening of the potassium channel in spinal cord attenuated the myocardial ischemia-reperfusion injury in SD rats,and the potassium channel in spinal cord was involved in the intrathecal morphine preconditioning-mediated cardioprotection against myocardial ischemia-reperfusion injury.2.The opened spinal cord neurons potassium channels attenuated the myocardial ischemia-reperfusion injury by inhibiting the harmful substances such as NGF,TRKA,TRPV1 and p-TRPV1.