Superoxide dismutase participates in p38 MAPK-mediated neuroprotection of limb ischemic preconditioning in global brain ischemic rats / 中国药理学与毒理学杂志

ABSTRACT

AIM To explore the role of superoxide dismutase (SOD) in the p38 mitogen-activated protein kinase (MAPK) mediated brain ischemic tolerance induced by limb ischemic preconditioning (LIP). METHODS The Wistar rats with permanent occlusion of the bilateral vertebral arteries were subjected to occlude the bilateral femoral arteries for 10 min, 3 times, at an interval of 10 min to get the LIP, then global brain ischemia was induced immediately by occluding the bilateral common carotid arteries for 8 min. SB 203580 (100 μmol·L-1, in a volume of 25 μL), an inhibitor of p38 MAPK, was intraventricularly injected 30 min before LIP in SB 203580+LIP+brain ischemia group. Xanthinoxidase and thiomalonylurea methods were used to determine SOD activity and malondialdehyde (MDA) content of the hippocampus, respectively. Thionin staining was used for observing histological changes of the hippocampus. RESULTS LIP significantly prevented the decrease of SOD activity, the increase of MDA content and the delayed neuronal death in the CA1 hippocampus induced by the brain ischemia. SB 203580 pretreatment evidently blocked the protective effect of LIP against the delayed neuronal death and the modulation on SOD activity and MDA content. CONCLUSIONSOD may play an important role served as a downstream molecule of p38 MAPK in the induction of brain ischemic tolerance by LIP.