Sufentanil postconditioning protects the myocardium from ischemia-reperfusion via PI3K/Akt-GSK-3β pathway.
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.
Anesthesiology Department, First Hospital Affiliated With China Medical University, Shenyang, China.
Qiao-ling
QL
Wu
Tu
T
Shen
Hong
H
Ma
Jun-ke
JK
Wang
D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006439:Hemodynamics; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017409:Sufentanil / Q000627:therapeutic use*
D017409:Sufentanil; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3