[Combined intervention of preconditioning and postconditioning against cerebral ischemia/reperfusion injury]

To investigate the protective effect of combined ischemic preconditioning and postconditioning against cerebral ischemia/reperfusion (I/R) injury and the potential mechanism.

Sixty SD rats were randomized into a sham operation group, a brain I/R group (model group), a brain I/R plus preconditioning group (preconditioning group), a brain I/R plus postconditioning group (postconditioning group), and a brain I/R plus preconditioning and postconditioning group (combined intervention group). The rat brain I/R injury model was created by suture emboli method. Preconditioning was induced by 3 cycles of 15 s occlusion followed by 30 s recanalization of the middle cerebral artery twice respectively at 24 h and 1 h before model creation, and postconditioning was elicited by 3 cycles of 30 s reperfusion followed by 15 s ischemia before long time reperfusion. The rats were sacrificed at 48 h after the reperfusion. The cerebral infarct volume and oxidative stress parameters as well as p-Akt and p-ERK1/2 protein expressions in the brain tissues were determined.

The cerebral infarct volumes showed no significant difference between the preconditioning group and the postconditioning group (P>0.05), but both were smaller than that in the model group and larger than that in the combined intervention group (all P values<0.01). In the model group, the level of oxidative stress was markedly increased (SOD activity increased and MDA level decreased), and both p-Akt and p-ERK1/2 protein expressions in the brain tissues were upregulated compared with those in the sham group (all P<0.01). Compared with the model group, the oxidative stress parameters presented no evident difference in preconditioning group (P>0.05), but p-Akt expression was slightly upregulated and p-ERK1/2 was remarkably down-regulated (P<0.05 and P<0.01) In the postconditioning group, the level of oxidative stress was significantly decreased, and p-Akt expression was dramatically increased with a mild down-regulation of p-ERK1/2 expression (P<0.01 and P<0.05). In the combined intervention group, the oxidative stress decrease the p-Akt expression rise and p-ERK1/2 expression inhibition were significantly greater than those in either the preconditioning group or the postconditioning group (all P values<0.01).

Combined treatment of preconditioning and postconditioning exerts stronger protective effect against cerebral I/R injury than either preconditioning or postconditioning alone. The mechanism is possibly due to the different but complementary protection of preconditioning and postconditioning against I/R injury.