摘要
目的观察低氧预适应(hypoxic preconditioning,HPC)降低脑中动脉阻塞(middle cerebral artery occlusion,MCAO)所致小鼠缺血性脑损伤的作用,探讨在HPC脑保护作用中p38丝裂原激活蛋白激酶(p38MAPK)的变化。方法60只健康雄性BALB/c小鼠(18g～22g,8周～10周)分为:常氧假手术组(H0sham),常氧缺血组(H0),HPC假手术组(H4sham)和HPC缺血组(H4),每组15只。运用整体低氧预适应模型和脑中动脉梗死缺血模型,结合神经行为学评价、氯化三苯基四氮唑(TTC)染色、免疫组织化学和蛋白印迹(Westernblotting)技术,观察HPC对小鼠脑缺血损伤的影响以及皮质组织内p38MAPK磷酸化水平和蛋白表达量的变化。结果研究发现,HPC可明显改善小鼠缺血后神经行为学表现,减小MCAO导致的鼠脑梗死面积,减轻半影区神经元的丢失,降低缺血区水肿率和密度值;与H0假手术组相比,缺血组小鼠皮质半影区p38MAPK磷酸化水平显著增高;与常氧缺血组小鼠皮质半影区相比,HPC缺血组小鼠皮质半影区内p38MAPK磷酸化水平增高更加明显。结论p38MAPK信号转导通路可能参与了HPC对小鼠局灶性缺血脑的保护作用。
Objective To observe the effect of hypoxic preconditioning （HPC） on middle cerebral artery occlusion （MCAO）- induced brain injury of mice and explore the change of p38 mitogen activated protein kinase （p38 MAPK） in neuroprotection of HPC. Methods Male BALB/c mice（18 g-22 g, 8 weeks-10 weeks） were randomly divided into H0 sham, H0, H4 sham and H4 groups. Using our unique hypoxic preconditioned mouse model and middle cerebral artery occlusion mouse model, combined with triphenyltetrazolium chloride（TFC） staining, neurological deficits evaluation, immunohistochemistry and Western blotting, the authors observed the changes of neurological score, brain infarct volume, neuronal injury, p38 MAPK phosphorylation and protein expression levels in the cerebral cortex of mice. Results HPC significantly decreased the neurological score, reduced infarction size, density of infarct area and edema ratio, and attenuated neuronal loss. Compared with the sham control, ischemia increased the phosphorylation levels of p38 MAPK significantly in penumbra of mouse brain. Furthermore, compared with the normoxic control, the phosphorylation levels of p38 MAPK increased more significantly in penumbra of HPC ischemic group. Conclusion p38 MAPK signal pathway might be involved in neuroprotective effect of HPC on focal ischemic brain of mice.
出处
《首都医科大学学报》
CAS
北大核心
2009年第5期643-647,共5页
Journal of Capital Medical University
基金
国家重点基础研究发展计划(973)(2006CB5041)
国家自然科学基金(30670782
30871219)
北京市自然科学基金A类项目(5072008)
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(PHR200906116)
北京市新世纪百千万人才工程培养经费(08-016)资助项目~~
关键词
低氧预适应
脑中动脉阻塞
P38丝裂原激活蛋白激酶
磷酸化水平
hypoxic preconditioning
middle cerebral artery occlusion
p38 mitogen activated protein kinase
phosphorylation
