Effect of morphine preconditioning on mitochondrial permeability transition pore after myocardial ischemia-reperfusion injury in rats / 中南大学学报(医学版)

ABSTRACT

Objective To investigate the effect of morphine preconditioning on mitochondrial permeability transition pore (MPTP) and its protective mechanism after myocardial ischemia-reperfusion injury. Methods A rat model of ischemia-reperfusion injury was established. Forty rats were injected with 2-3[H] DOG and then divided into 4 groups randomly a sham operation (S) group, an ischemia-reperfusion injury (IR) group, a morphine preconditioning (Mp+IR) group, and a cyclosporine A preconditioning (CsA+IR) group. We monitored the concentrations of serum creatine kinase-Mb (CK-Mb) and cardiac troponin I (cTnI), and measured myocardial mitochondrial 2-3[H] DOG, cytochrome c content, Ca2+ concentration ([Ca2+]m), the velocity of Ca2+ intake and reaction half time of mitochondrial permeability transition pore (MPTP t1/2) in the 4 groups. Results The concentrations of serum CK-Mb and cTnI decreased more in the Mp+IR group and the CsA+IR group than those of the IR group. The concentrations of 2-3[H]DOG and [Ca2+]m in the IR group were evidently higher but the level of cytochrome c was lower than those of the sham operation group. The concentrations of 2-3[H] DOG and [Ca2+]m in the Mp+IR group decreased whereas the concentration of cytochrome c increased compared with those in the IR group. Mitochondrial 2-3[H]DOG content was positively correlated with the concentration of calcium (r=0.797, P<0.01). The 2-3[H]DOG and [Ca2+]m content were negatively correlated with cytochrome c in the IR group (r=-0.805 and r=-0.648, respectively, P<0.01). MPTP t1/2 in the IR group was shortened evidently, and that in the Mp+IR and CsA+IR group was significantly lengthened. Conclusion Morphine preconditioning may have myocardial protective effect through unburdening the calcium overload and lengthening the MPTP t1/2.