低氧预适应保护缺血脑组织效应中CaMKⅡ的作用机制  

Mechanisms of CaMK Ⅱin the Hypoxic Preconditioning Protection of Ischemic Brain Tissue

作　　者：李海涛[1] 卜祥宁[2] 江君[2] 杨巍巍[2] 李俊发[2] 

机构地区：[1]首都医科大学燕京医学院生理教研室,101300 [2]首都医科大学神经生物系北京神经科学研究所

出　　处：《天津医药》2013年第2期142-144,共3页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30871219);北京市自基金A类项目(项目编号:5072008)

摘　　要：目的探讨钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)在低氧预适应(HPC)保护小鼠缺血脑组织中的作用。方法36只健康雄性BALB/c小鼠随机分为常氧假手术组、HPC假手术组、常氧缺血组和HPC缺血组,每组6只应用Western blot并结合Gel Doc凝胶成像系统定量检测4组小鼠脑组织内CaMKⅡ蛋白表达量和磷酸化水平的变化,用免疫组化检测常氧缺血组和HPC缺血组小鼠脑皮层CaMKⅡ磷酸化水平。结果与常氧假手术组相比,常氧缺血组小鼠皮层缺血核心区和半影区CaMKⅡ蛋白表达量和磷酸化水平均显著降低(P<0.05),HPC缺血组缺血半影区CaMKⅡ磷酸化水平及p-CaMKⅡ阳性细胞数目高于常氧缺血组(P<0.05)。结论HPC减缓缺血半影区CaMKⅡ磷酸化水平的降低,可能参与减轻因中脑动脉闭塞所致小鼠缺血性脑损伤作用。Objective To investigate the effect of hypoxic preconditioning （HPC） on middle cerebral artery occlusion （MCAO）-induced brain injury in mice, and changes of calcium/calmodulin-dependent protein kinase II （CaMK Ⅱ ） phosphory- lation thereof. Methods Thirty-six healthy male BALB/c mice were randomly divided into 4 groups： the normoxic sham sur- gery （HO-sham） group, HPC-sham group, HO-ischemia group and HPC-ischemia group. Changes of CaMK Ⅱ phosphoryla- tion in the brain of mice were detected by Western blot combined with Gel Doc imagine systems. Levels of CaMK Ⅱ phos- phorylation in brain cortex of mice were detected by immunohistochemistry. Results Both phosphorylation and protein ex- pression levels in the ischemic core and penumbra were significantly decreased in HO-ischemia group compared with those in HO-sham group （P〈 0.05）. But the phosphorylation levels of CaMK Ⅱ and the positive cell number ofp - CaMK Ⅱ in the pen- umbra were significantly higher in HPC-ischemia group than those of HO-ischemia group （P 〈 0.05）. Conclusion The de- creased CaMK Ⅱ phosphorylation level in ischemia penumbra might involve in the attenuation of middle cerebral artery occlu- sion （MCAO）-induced brain injury in mice.

关 键 词：钙-钙调素依赖性蛋白激酶2型 缺氧 脑缺血 氧化磷酸化 梗死 大脑中动脉 低氧预适应 

分 类 号：R743.3[医药卫生—神经病学与精神病学]