?-endorphin Mediated RVLM Morphine Preconditioning Reduces Myocardial Ischemia-reperfusion Injury In Rats

Objective To investigate the effect of morphine preconditioning in rostral ventrolateral medullar(RVLM)on myocardial ischemia-reperfusion(I/R)injury in rats and the changes of ?-endorphin(?-EP)contents in T2-5 spinal cord and left ventricular muscle during this process.Methods 72 adult male SD rats were randomly divided into 4 groups(n=18 in each group): sham-operated group(Sham group),ischemia-reperfusion group(IR group),ischemic preconditioning group(IPC+IR group),and RVLM morphine preconditioning group(MPC +IR group).The ischemia reperfusion(I/R)model was treated with coronary artery left anterior descending branch ligation for 30 min and then reperfusion for 120 min.The ischemic preconditioning(IPC)was myocardial ischemia for 5 min,reperfusion for 5 min,and repeated above operations for 3 times.Sham group,IR group and IPC group were injected 0.9% saline 0.2 ?l in advance through catheter in 5 min.After 5 min interval,0.9% saline was infused again and repeated 3 times for a total of 0.6 ?l.Then I/R was performed in the IR group;IPC was performed before I/R in the IPC group;in the MPC+IR group,morphine was injected before I/R(0.2 ul at a constant speed within 5 min,then pause for 5 minutes,repeat twice and total infusion of 0.6 ul,morphine was prepared with saline at 1 ug/kg to make 0.6 ul).The numbers of ventricular arrhythmias [premature ventricular contraction(PVCs)and ventricular tachycardia/ ventricular fibrillation(VT/VF)] were recorded within 30 min of reinfusion by electrocardiogram monitoring.Cardiac specimens were stained with TTC.Left ventricle(LV),right ventricle(RV),infarct area(IS),ischemic risk area(AAR)volume were measured,and the IS/AAR ratio was calculated.Western blot assay was used for RVLM nucleus c-fos protein expression detection.ELISA assay and immunohistochemical staining assay were used for quantitative and qualitative detection the levels of ?-EP expression in T2-5 spinal cord and left ventricular muscle,respectively.Results Compared with the Sham group,the IS volume,IS/AAR,the numbers of PVCs,VT/VF,and expression of c-Fos in RVLM and ?-EP in spinal cord and myocardium were increased in IR group(P<0.01).Compared with IR group,the IS volume,IS/AAR,the numbers of PVCs,VT/VF,and the levels of c-Fos expression were significantly decreased(P < 0.01),but the levels of ?-EP expression in myocardium and spinal cord were significantly increased in IPC+IR group and MPC+IR group(P < 0.01).Conclusion Morphine preconditioning in RVLM can alleviate myocardial I/R injury in rats,which may be related to the decrease of c-Fos expression in RVLM nucleus after I/R.?-endorphin may be involved as a transmitter in the myocardial protective effect of morphine preconditioning in RVLM.