超氧化物岐化酶参与p38 MAPK介导的肢体缺血预处理对大鼠全脑缺血的保护作用

摘要

目的 探讨超氧化物岐化酶(SOD)在p38有丝分裂素激活蛋白激酶(MAPK)介导的肢体缺血预适应(LIP)脑保护中的作用.方法 永久凝闭椎动脉的Wistar大鼠,重复夹闭双侧股动脉3次(每次10 min,间隔10 min)作为LIP,之后即刻夹闭双侧颈总动脉8 min造成全脑缺血.SB 203580+LIP+脑缺血组于LIP前30 min侧脑室内注射p38 MAPK抑制剂SB 203580 (100 μmol·L-1, 25 μL).黄嘌呤氧化酶法测定海马SOD活性,硫代巴比妥酸法测定海马丙二醛(MDA)含量,硫堇染色观察海马的组织学分级.结果 LIP显著抑制脑缺血引起的海马CA1区SOD活性下降、MDA含量增加及延迟性神经元死亡.预先侧脑室注射SB 203580显著阻断LIP对缺血脑组织的上述保护作用.结论 SOD可能作为p38 MAPK的下游分子参与LIP诱导的脑缺血耐受.%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.