关键词: 低氧预适应, 大脑中动脉阻塞, 丝裂原和应激激活的蛋白激酶1, cAMP反应元件结合蛋白, 脑保护

Abstract: Objective To explore the role of mitogen- and stress-activated protein kinase 1 (MSK-1) and cAMP response element binding protein (CREB) in hypoxic preconditioning (HPC)-induced neuroprotection against cerebral ischemic injuries. Methods Healthy adult male BALB/c mice weighing 18～22g were randomly divided into 4 groups as follows: normoxia sham (NS), HPC sham (HS), normoxia ischemia (HI) and HPC ischemia (HI). Using HPC and middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia mouse models, and the techniques of triphenyltetrazolium chloride (TTC) staining, neurological deficits evaluation and Western blot, we observed the neurological scores, brain infarct volume, the phosphorylation and protein expression levels of MSK-1 and CREB in regions of ischemic cortex. Results HPC attenuated MCAO-induced neurological deficits, and decreased brain infarct volume and edema ratio of mice. The phosphorylation levels of MSK-1 and CREB decreased significantly (p<0.05, n=4) in the ischemic core, while HPC could promote significantly (p<0.05, n=4) both MSK-1 and CREB phosphorylation levels in penumbra of MCAO-induced ischemic cortex. However, there were no significant changes of total MSK-1 and CREB protein expressions in the ischemic regions of MCAO-treated HPC mice. Conclusion The increased MSK-1 and CREB phosphorylations in ischemic penumbra were involved in HPC-induced neuroprotection against cerebral ischemic injuries of mice.

Key words: Hypoxic preconditioning (HPC), Middle cerebral artery occlusion (MCAO), MSK-1, CREB, Neuroprotection