MSK-1和CREB参与低氧预适应降低小鼠缺血性脑损伤  

MSK-1 and CREB are involved in HPC-induced neuroprotection against cerebral ischemic injuries of mice

作　　者：杜建丽[1] 梁婧[1] 李沫音[1] 张旭[1] 赵丽[1] 罗艳琳[1] 李俊发[1] 

机构地区：[1]首都医科大学神经生物学系北京神经科学研究所,北京100069

出　　处：《基础医学与临床》2010年第11期1143-1148,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30871219);国家重点基础性研究项目(2006CB5041);北京市教育委员会科技计划重点项目(KZ200810025012);北京市属高等学校人才强教计划项目(京教人[2008]17号);北京市新世纪百千万人才工程培养经费(08-016);教育部高等学校博士点科研基金(20091107110001)

摘　　要：目的探讨丝裂原和应激激活蛋白激酶1(MSK-1)及cAMP反应元件结合蛋白(CREB)在低氧预适应(HPC)保护小鼠缺血脑组织中的作用。方法将健康成年雄性BALB/c小鼠随机分为4组:常氧假手术组(NS)、HPC假手术组(HS)、常氧缺血组(NI)和HPC缺血组(HI)。利用已建整体HPC和大脑中动脉阻塞(MCAO)小鼠模型,并结合神经行为学评价、氯化三苯基四氮唑(TTC)染色和蛋白印迹(Western blot)等技术,观察HPC对小鼠脑缺血损伤的影响,检测小鼠脑皮层不同缺血区域内MSK-1和CREB磷酸化水平和蛋白表达量的变化。结果 HPC可明显改善小鼠脑缺血后神经行为学表现,减小MCAO致脑缺血皮层梗死体积和水肿率;MCAO致小鼠脑局部皮层缺血后,其缺血核心区内MSK-1和CREB磷酸化水平明显下降(P<0.05);HPC可明显增加缺血半影区内MSK-1和CREB磷酸化水平(P<0.05),而MSK-1和CREB总蛋白表达量在缺血核心区和半影区内均无明显改变。结论 HPC可能通过提高缺血半影区内MSK-1及其底物CREB的磷酸化水平来降低小鼠缺血性脑损伤。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 male BALB/c mice 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 level of MSK-1 and CREB in regions of ischemic cortex.Results HPC attenuated MCAO-induced neurological deficits,and decreased brain infarctvolume and edema ratio of mice.The phosphorylation level of MSK-1 and CREB decreased significantly（P0.05,n=4） in the ischemic core,while HPC could promote significantly（P0.05,n=4） both MSK-1 and CREB phosphorylation level in penumbra of MCAO-induced ischemic cortex.However,there was no significant change 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.

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 

分 类 号：R741[医药卫生—神经病学与精神病学]