The Experimental Study On Role Of PI3K-Akt/eNOS Activity In The Effect Of Remote Postconditioning Induce By Brief Pulmonary Ischemia In Rabbits

Objective:Brief pulmonary ischemia was induced as remote postconditioning before the onset of myocardial ischemic-reperfusion in vivo rabbit model in order to evaluate the protection effects of remote postconditioning. The role of pathway of PI3K/eNOS was analysised at the same time.Methods:Thirty rabbits were randomized into 3 groups: group control (group C), remote postcondi- tioning group (group RIP) and therapeutic group with L-NAME (groupL). Anesthetized rabbits were subjected to 30 min occlusion of left anterior descending coronary artery (LAD) followed by 180 min reperfusion in group C (n=10). The left pulmanary artery was blocked 3 min followed by 3 min reperfusion while LAD was occluded 24 min and then reperfused 180 min in group RIP (n=10). In group L(n=10), the left pulmanary artery was blocked 3 min followed 3 min reperfusion while LAD was occluded 24 min and while intravenous infusion of L-NAME (10mg/kg) was done while LAD was occluded 27 min, then 180 min reperfusion of LAD was followed. Blood samples were harvested from internal jugular vein at three time points (before occlusion, before reperfusion, at the end of test) respectively to analysis the activity of superoxide dismutase (SOD), the concentration of maleic dialdehyde (MDA) and creatine kinase (CK). Myocardial tissue samples were taken at the end of test to analysis the expression of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) by immunohistochemisty and to calculate the cardiomyocyte apoptosis index (AI) by TUNEL. Pulmanary tissue samples were harvested at the end of test by hematoxylin and eosin stain to evaluate the damage of lung induced by brief pulmonary ischemia-reperfusion.Result:There was no significant difference among three groups in the activity of SOD or the concentration of MDA and CK before occlusion and before reperfusion (P>0.05). At the end of test, the activity of SOD was higher in group RIP than in gourp C (P<0.05) or group L (P<0.05), the concentration of MDA was lower in group RIP than in gourp C (P<0.05) or group L (P<0.05), the concentration of MDA was lower in group RIP than in gourp C (P<0.05) or group L (P<0.05). But there was no significant difference between group C and group L in activity of SOD, concentration of MDA and CK at the end of test.The Akt experssion in myocardial tissue was significantly increased in group RIP than gourp C or group L (P<0.05), respectively. The eNOS experssion in myocardial tissue was also significantly increased in group RIP than gourp C or group L (P<0.05). The cardiomyocyte apoptosis index was significantly lower in group RIP than gourp C or group L (P<0.05), respectively.Pulmonary injury including interstitial edema and hyperemia of alverolar was not observed in left and right pulmonary tissue.Conclusions:Brief pulmanary occlusion-reperfusion induced as remote postconditioning might attenuate myocardial ischemia-reperfusion injury. The protective effects of remote postconditioning may be acted by the activation of pathway of PI3K/Akt/ eNOS. Brief pulmonary ischemia-reperfusion is safe to the function of lung. The lung used as remote organ would be studied more in the future.