Role of adiponectin/phosphatidylinositol 3-kinase/protein kinase B signaling pathway on limb ischemic preconditioning on myocardial protection

摘要

The adiponectin/phosphatidylinositol 3-kinase/protein kinase B (ADP/PI3k/Akt) signal transduction pathway has an important role in promoting cell survival. This study was designed to determine if the ADP/PI3K/Akt signaling pathway has a role in the mechanism of ischemia–reperfusion injury in vivo. Sprague–Dawley rats were divided into five groups of six: Group A was the sham group, group B was the myocardial ischemia–reperfusion injury (MIRI) group; the left anterior descending coronary artery (LAD) was ligated and, after 30 min of ischemia, reperfusion was conducted for 120 min, group C was the limb ischemia preconditioning (LIPC) group; the femoral artery was blocked continuously for 5 min, and sustainable reperfusion was carried out for 5 min, and this procedure was repeated thrice. The MIRI experiment was carried out on the fourth day after consecutive preconditioning for 3 days. The surgical procedure was the same as with the MIRI model. Group D was the LY294002 pretreatment group: 15 min before reperfusion, ischemic rats underwent pretreatment with LY294002. The final group was the LIPC+LY294002 group; after limb ischemia preconditioning, rats underwent LY294002 pretreatment 15 min before reperfusion. Expression of ADP and adiponectin receptor 1 (ADPR1) messenger ribonucleic acid (mRNA), PI3k and p-Akt protein increased significantly in the myocardial tissue of the LIPC group in comparison with that in the sham group. This finding suggests that limb ischemic preconditioning increased the expression of ADP in the myocardial tissue of rats with myocardial ischemia–reperfusion injury. It also demonstrated that ADP activated PI3k by the ADP/PI3k/Akt signaling pathway to increase the phosphorylation of the effector protein Akt.