PI3K/Akt signaling pathway mediates the protective effect of endomorphin-1 postconditioning against myocardial ischemia-reperfusion injury in rats

Abstract

To investigate the role of PI3K/Akt signaling pathway in mediating the protective effect of endomorphin-1 against myocardial ischemia-reperfusion (IR) injury. Fifty SD male rats were randomly divided into sham operation group, myocardial IR group, endomorphin-1 post-treatment group (EM50 group), endomorphin-1+wortmannin (a PI3K/Akt signaling pathway inhibitor) treatment group (EM50+Wort group), and wortmannin treatment group (Wort group). Rat models of myocardial IR injury were established by ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The heart rate and mean arterial pressure were monitored during the experiment. Plasma levels of LDH, CK-MB, cTnI, IL-6, TNF-α, SOD and MDA were measured after reperfusion. The mRNA expression of Bax and Bcl-2 was detected using RT-PCR, and the expression of apoptosis-related protein cleaved caspase-3, phosphorylated Akt protein and total Akt protein in myocardial tissue was detected using Western blotting. Myocardial IR injury significantly decreased heart rate and blood pressure of the rats in comparison with the sham operation (P < 0.05). Compared with those in the IR group, the rats in EM50 group showed significantly increased heart rate and blood pressure (P < 0.05) with decreased plasma LDH, CK-MB, cTnI, IL-6, TNF-α and MDA levels (P < 0.05), increased SOD activity (P < 0.05), increased expression of p-Akt protein and Bcl-2 mRNA (P < 0.05), and decreased expression of Bax mRNA and cleaved caspase-3 protein (P < 0.05). In EM50+Wort group, the heart rate and blood pressure were significantly lowered (P < 0.05), plasma LDH, CK-MB, cTnI, IL-6, TNF-α and MDA levels increased (P < 0.05), SOD activity decreased (P < 0.05), the expression of p-Akt protein and Bcl-2 mRNA was reduced (P < 0.05), and the expression of Bax mRNA and cleaved caspase-3 protein increased (P < 0.05) as compared with those in EM50 group. EM-1 postconditioning can regulate cardiac myocyte apoptosis and reduce myocardial IR injury in rats. The PI3K/Akt signaling pathway may play a role in mediating the myocardial protective effects of EM-1 postconditioning.