Jin Rui-Li, Li Wen-Bin, Li Qing-Jun, Zhang Min, Xian Xiao-Hui, Sun Xiao-Cai, Zhao Hong-Gang, Qi Jie
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang 050017, PR China.
Neurosci Res. 2006 May;55(1):65-73. doi: 10.1016/j.neures.2006.01.006. Epub 2006 Mar 13.
To clarify the role of phosphorylated extracellular signal-regulated kinases (pERK1/2) in the neuroprotection of limb ischemic preconditioning (LIP) in rats, we investigated the expression of pERK1/2 using Western blot and flow cytometry in the hippocampus after LIP and the effect of pERK1/2 inhibitor PD 98059 on the neuroprotection of LIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by severe ischemic insult. It demonstrated that pERK1/2 in the hippocampus increased after LIP. In the CA1 hippocampus, ERK1/2 activation began to increase at 6h and reached peak at 12h after LIP, and decreased to sham level at 5d after LIP. On the other hand, in the CA3/DG, pERK1/2 enhanced at 1d, reached peak at 3d, and lasted to 5d after LIP. Pretreatment with PD 98059 before LIP blocked the neuroprotection of LIP in a dose-dependent manner. These findings supported that the upregulation of pERK1/2 in the CA1 hippocampus contributed to the neuroprotection of LIP against DND normally caused by the brain ischemic insult.
为阐明磷酸化细胞外信号调节激酶（pERK1/2）在大鼠肢体缺血预处理（LIP）神经保护中的作用，我们采用蛋白质免疫印迹法和流式细胞术研究了LIP后海马中pERK1/2的表达，以及pERK1/2抑制剂PD 98059对LIP抗严重缺血损伤正常诱导的海马CA1区迟发性神经元死亡（DND）神经保护作用的影响。结果表明，LIP后海马中pERK1/2增加。在海马CA1区，LIP后6小时ERK1/2激活开始增加，12小时达到峰值，LIP后5天降至假手术水平。另一方面，在CA3/DG区，pERK1/2在LIP后1天增强，3天达到峰值，并持续至5天。LIP前用PD 98059预处理以剂量依赖方式阻断了LIP的神经保护作用。这些发现支持海马CA1区pERK1/2的上调有助于LIP抗脑缺血损伤正常引起的DND的神经保护作用。
