Role of free radicals in cerebral ischemic tolerance of rats induced by limb ischemic preconditioning / 中国病理生理杂志

ABSTRACT

AIM: To explore whether free radicals participate in cerebral ischemic tolerance and the up-regula-tion of p38 MAPK and ERK signaling pathways in rats induced by limb ischemic preconditioning (LIP). METHODS: A total of 128 Wistar rats with permanent occlusion of bilateral vertebral arteries were randomly divided into sham group (n=16), cerebral ischemia (CI) group (n=16), LIP+CI group (n=16), DMTU (a free radical scavenger)+LIP+CI group (n=64) and DMTU+sham group (n=16). Six rats in each group were used to observe the delayed neuronal death (DND) in hippocampal CA1 region by thionin staining at 7 d after the end of operation. Other 10 rats in each group were used to de-tect the expression of p38 MAPK and ERK in hippocampal CA1 region by immunohistochemistry and Western blot. RE-SULTS Lethal CI resulted in obvious DND in hippocampal CA1 region. However, LIP reversed the above injurious changes, represented by the decrease in histological grade and the increase in neuronal density compared with CI group (P<0. 01). Moreover, LIP significantly up-regulated the expression of p38 MAPK and ERK in hippocampal CA1 region com-pared with CI group (P<0. 01). Administration of free radical scavenger DMTU via femoral vein before LIP partially re-versed the neuroprotective effect of LIP, and blocked the up-regulation of p38 MAPK and ERK expression in hippocampal CA1 region in rats compared with LIP+CI group (P<0. 01). CONCLUSION: Free radicals are involved in the neuropro-tection and up-regulation of p38 MAPK and ERK expression induced by LIP in rats.