| Background: Myocardial ischemia reperfusion injury(MIRI),which is often occurred in the treatment of ischemic heart disease,is a common urgent pathophysiological phenomenon.Researches showed that the endomorphin-1(EM-1)postcondition could alleviate the myocardial ischemia reperfusion injury by stimulating ?-opioid receptors,but the specific mechanism was not clear.Extracellular regulated protein kinases(ERK1/2)pathway was involved in cell survival,apoptosis and proliferation activity in the body,which belongs to the reperfusion injury salvage kinase pathway(Reperfusion injury salvage kinase,RISK).ERK1/2 played an important role in protecting the myocardium during myocardial ischemia-reperfusion.Studies showed that phosphorylation of ERK1 / 2 in the early stage of myocardial reperfusion injury has a cardioprotection.Meanwhile mitochondrial permeability transition pore(MPTP)was an end effector of postconditioning and a key point of MIRI,there is no relevant article reports about whether the opening of MPTP was affected during the process of EM-1postconditioning.Objective: To investigate whether the ERK1/2 pathway was activated and the opening of MPTP was regulated during the process of EM-1 postconditioning by giving the ERK1/2 signal pathway inhibitor PD98059 and mitochondrial permeability transition pore(MPTP)opener Atractyloside.Methods: Rats were divided into 7 groups(S group,IR group,EM50 group,group,EM50+PD group,PD group,Atr group,EM50+Atr group),rat myocardial ischemia reperfusion model was constructed by ligating the left anterior descending coronary artery for 30 min and keeping reperfusing for 120 min,at the same time,hemodynamics were detected.After reperfusion,blood was collected from rat common carotid artery,serum was separated and used to test myocardial enzyme indicators(CK-MB?LDH?CTn I)and biochemical indexes(IL-6?TNF-??Cyt-C?SOD?MDA).The area of myocardial infarction was measured by the method of TTC double staining(n=5),and the bioelectric morphological changes of myocardial tissues were detected by HE staining(n=4),Western-blot was used to detect the expression of ERK1/2?P-ERK1/2?Cleaved Caspase-3?Bax?Bcl-2 protein of each treatment group(n=3).Results:(1)Compared with IR group,the content or activity of LDH,MDA,CK-MB,CTn I,TNF-?,IL-6 decreased(P<0.05),the activity of SOD increased(P<0.05)in EM50 group;compared with EM50 group,the content or activity of LDH,MDA,CK-MB,CTn I,TNF-?,IL-6 increased(P<0.05),the activity of SOD decreased(P<0.05)in both EM50+PD group and EM50+Atr group;(2)Compared with IR group,heart function of EM50 group was improved;compared with EM50 group,EM50+PD group and EM50+Atr group have poorer heart function;(3)Compared with IR group,the myocardial infarct size of EM50 group decreased(P<0.05),and EM50 group showed the lightest pathological changes;compared with EM50 group,the myocardial infarct size of EM50+PD group and EM50+Atr group increased and showed heavier pathological changes;(4)Compared with IR group,the expression of P-ERK and Bcl-2 increased(P<0.05),and the expression of Bax and Cleaved Caspase-3 decreased(P<0.05)in EM50 group;compared with EM50 group,the expression of P-ERK and Bcl-2 decreased(P<0.05),and the expression of Bax and Cleaved Caspase-3 increasedin EM50+PD group and EM50+Atr group(P<0.05).Conclusion:(1)Endomorphine-1 postconditioning have protective effect on myocardial icshemia reperfusion injury,which might be attributable to the activation of the ERK1/2 pathway;(2)Endomorphine-1 may protect the heart via the inhibition of MPTP opening during postconditioning. |
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