Role of nitric oxide in the protective effect of morphine postconditioning against ischemia-reperfusion-induced myocardial apoptosis / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of nitric oxide (NO) in the protective effects of morphine postconditioning against ischemia-reperfusion (I/R)-induced myocardial apoptoais. Methods Sixty pathogen-free SD rats were randomly divided into 4 groups ( n = 15 each) group Ⅰ sham operation (S) ; group Ⅱ I/R; group Ⅲ morphine postconditioning ( M ) and group Ⅳ M + L-NAME ( non-selective NOS inhibitor). The animals were anesthetized with intraperitoneal pentobarbital 60 mg/kg, tracheostomized and mechanically ventilated. ECG was monitored. Right carotid artery was cannulated for BP monitoring and left jugular vein was cannulated for drug and fluid administration. Myocardial ischemia was induced by 45 min occlusion of left anterior descending coronary artery (LAD) followed by 120 min reperfusion. In group S LAD was exposed but not occluded; in group M morphine 1.25 mg/kg was injected iv over 5 min from 3 min before reperfuaion to 2 min of repeffuaion and in group M + L-NAME L-NAME 10 mg/kg was injected iv at 20 min before myocardial ischemia. Hemodynamic changes were monitored. The animals were killed at the end of 120 min reperfusion and their hearts removed. Myocardial apoptosis was determined by TUNEL technique. The expression of Akt phosphorylation was assessed by Western blotting. The NO content in myocardium was measured by a chemiluminescence detector.Results A large number of TUNEL positive cells (18.4 ± 1.1 ) % were observed in group I/R. Morphine postconditioning exerted a significant anti-apoptotic effect. The number of TUNEL positive cells was reduced to (10.8 ± 1.2)%. The myocardial eNOS phosphorylation expression and NO content were significantly increased in group M as compared with group I/R. The anti-apoptofie effect and increased NO production were significantly reversed by L-NAME. However, pretreatment with L-NAME did not inhibit the phosphorylation of eNOS in group L + M. Conclusion In vivo, morphine postconditioning can significantly reduce I/R-induced myocardial apoptosis through phosphorylation of eNOS and increase in NO production.