Effects of ischemic preconditioning on oxidative stress and mitochondrial function in young and old rat myocardium with ischemia/reperfusion / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM: To study the protective effect of ischemia preconditioning ( IPC ) on ischemia/reperfusion ( IR)-damaged myocardium in young and old rats .METHODS: Male Wistar rats aged at 3 months ( young ) and 20 months ( old) were used to establish myocardial IPC model and IR model with the method of Langendorff heart perfusion . The rats were divided into young ischemia/reperfusion ( YIR) group, young ischemic preconditioning ( YPC) group, old ischemia/reperfusion ( OIR) group and old ischemic preconditioning ( OPC) group.Transmission electron microscopy was used to observe the ultrastructural changes of myocardial tissue and myocardial mitochondria .The myocardial infarction area was determined by TTC staining .The lactate dehydrogenase ( LDH) content in coronary effluent fluid and the levels of su-peroxide dismutase ( SOD) and malondialdehyde ( MDA) in myocardial tissues were detected by the method of colorimetry . The levels of nitrated and carbonylated proteins in myocardial tissue were measured by ELISA .The myocardial cell apopto-sis was analyzed by TUNEL assay .The mitochondrial respiratory function and mitochondrial permeability transition pore o-pening induced by calcium load were evaluated by oxygen electrode method .RESULTS: Compared with YIR group , the myocardial infarction area in YPC group was obviously smaller , SOD activity in myocardial tissues increased , LDH activity in coronary effluent fluid and the content of MDA decreased , and the levels of nitrated and carbonylated proteins in the car-diac tissues reduced .In YPC group, the mitochondrial membrane structure appeared intact , cristae of the mitochondria showed close arrangement , and the matrix was compressed under the electron microscope .Myocardial mitochondrial respir-atory control rate , state Ⅲoxygen consumption and the P/O ratio in YIR group all significantly increased , proton leak de-creased, mitochondrial swelling induced by calcium distinctly reduced , and myocardial apoptosis rate declined .No signifi-cant difference of the above indexes between OIR group and OPC group was observed .Compared with YPC group , myocar-dial ultrastructural damage increased clearly , cardiac oxidative stress increased , mitochondrial respiratory function de-clined, and cell apoptosis and necrosis increased in OPC group .CONCLUSION:Ischemic preconditioning has protective effect against myocardial IR injury in young rat hearts , while old rat hearts were less sensitive to ischemic preconditioning , leading to bluntness of cardioprotection with IPC in aging hearts .This may be related to mitochondrial injury and severe cel-lular apoptosis caused by increase of cardiac oxidative stress levels in the aging ischemic preconditioning heart .