Qiao-ling Wu1, Tu Shen, Hong Ma, Jun-ke Wang. 1. Anesthesiology Department, First Hospital Affiliated With China Medical University, Shenyang, China.
Abstract
BACKGROUND: Previous studies have shown that opioid postconditioning reduces apoptosis through antiapoptotic signaling. The present study evaluated whether sufentanil could induce cardioprotection after ischemia-reperfusion (I/R) and whether the PI3K/Akt-GSK-3β pathway modulates antiapoptotic proteins in sufentanil postconditioning. METHODS: We subjected male Sprague-Dawley rats to 30 min of myocardial ischemia and 2 h of reperfusion. We randomized rats into seven groups: sham, I/R, sufentanil postconditioning (I/R+sufen), sham plus sufentanil (sham+sufen), sham plus 15 μg · kg(-1) intravenous wortmannin (PI3K inhibitor), I/R plus wortmannin, and sufentanil plus wortmannin. We induced sufentanil postconditioning with 3 μg · kg(-1) sufentanil for 3 min in the beginning of reperfusion after 30 min ischemia. We assessed hemodynamics, myocardial infarct size, number of apoptotic cardiomyocytes, total Akt and GSK-3β, phosphorylated Akt and GSK-3β, caspase-3, Bax, and Bcl-2 protein expression. RESULTS: The I/R+sufen group had significantly reduced infarct size compared with the I/R group (23.3% ± 9.0% versus 50.1% ± 7.4%; P < 0.05). The apoptotic index of cardiomyocytes was significantly reduced with sufentanil treatment (20.0% ± 3.5%) compared with the I/R group (47.0% ± 6.3%; P < 0.05). The I/R+sufen group reduced the expression of protein-cleaved caspase-3 and Bax, and increased Bcl-2, phosphorylated Akt, and GSK3β compared with the I/R group. Wortmannin eliminated the cardioprotection produced with sufentanil treatment. CONCLUSIONS: Sufentanil postconditioning can induce myocardial protection by activating the PI3K/Akt-GSK-3β pathway and modulating Bax and Bcl-2 expression.
BACKGROUND: Previous studies have shown that opioid postconditioning reduces apoptosis through antiapoptotic signaling. The present study evaluated whether sufentanil could induce cardioprotection after ischemia-reperfusion (I/R) and whether the PI3K/Akt-GSK-3β pathway modulates antiapoptotic proteins in sufentanil postconditioning. METHODS: We subjected male Sprague-Dawley rats to 30 min of myocardial ischemia and 2 h of reperfusion. We randomized rats into seven groups: sham, I/R, sufentanil postconditioning (I/R+sufen), sham plus sufentanil (sham+sufen), sham plus 15 μg · kg(-1) intravenous wortmannin (PI3K inhibitor), I/R plus wortmannin, and sufentanil plus wortmannin. We induced sufentanil postconditioning with 3 μg · kg(-1) sufentanil for 3 min in the beginning of reperfusion after 30 min ischemia. We assessed hemodynamics, myocardial infarct size, number of apoptotic cardiomyocytes, total Akt and GSK-3β, phosphorylated Akt and GSK-3β, caspase-3, Bax, and Bcl-2 protein expression. RESULTS: The I/R+sufen group had significantly reduced infarct size compared with the I/R group (23.3% ± 9.0% versus 50.1% ± 7.4%; P < 0.05). The apoptotic index of cardiomyocytes was significantly reduced with sufentanil treatment (20.0% ± 3.5%) compared with the I/R group (47.0% ± 6.3%; P < 0.05). The I/R+sufen group reduced the expression of protein-cleaved caspase-3 and Bax, and increased Bcl-2, phosphorylated Akt, and GSK3β compared with the I/R group. Wortmannin eliminated the cardioprotection produced with sufentanil treatment. CONCLUSIONS:Sufentanil postconditioning can induce myocardial protection by activating the PI3K/Akt-GSK-3β pathway and modulating Bax and Bcl-2 expression.