Apoptotic inhibition is involved in protection of combining morphine and limb remote ischemic postconditioning against myocardial ischemia/reperfusion injury

Objective To evaluate the role of anti-apoptosis in protection of combined morphine and limb remote ischemic postconditioning(RIP) against myocardial ischemia/reperfusion injury(I/RI). Methods Sixty male SD rats were randomly allocated into four groups(n=15): ischemia/reperfusion(I/R) group(group I/R), group RIP, morphine group (group M), and combined morphine and RIP group(group M+RIP) . The apoptosis in the myocardial ischemic core, ischemic border and non-ischemic areas were assessed through the Tunel assay and real-time PCR for Bax mRNA and Bcl-2 mRNA. Optical and electronic microscopes were used to determine the cardiomyocyte morphology. Results The apoptotic index(AI) of myocytes in the ischemic core area was (49.1±4.9)%, (34.2±2.9)%, (39.7±3.2)% and (29.0±4.9)% in the I/R, RIP, M, M+RIP groups, respectively. The AI of myocytes in the ischemic border area was(12.7±2.2)%, (8.2±1.6)%, (10.4±2.7)% and (5.9±1.4)% in the I/R, RIP, M, M+RIP groups, respectively. In the ischemic core and border area, the AI of myocytes was significantly decreased in the M+RIP group compared to that in the I/R and M groups(P<0.05),the expression of Bcl-2 mRNA was significantly increased(P<0.05) and expression of Bax mRNA was significantly decreased in group M+RIP(P<0.05), compared to that in the I/R, RIP, and M groups. Bcl-2/Bax ratio was significantly increased in group M+RIP(P<0.05), compared to that in the I/R, RIP, and M groups. Optical and electronic microscopes showed that myocardial morphology and mitochondrial structures were significantly improved in group M+RIP. Conclusions Apoptotic inhibition by Bcl-2 linked signaling pathway is one of the mechanisms of cardioprotection by combining morphine and limb RIP against I/RI. Key words: Ischemia/reperfusion injury; Limb remote ischemic; Morphine; Postconditioning; Apoptosis; Cardioprotection