P38MAPK磷酸化水平增高参与HPC降低MCAO所致小鼠缺血性脑损伤  

Increased phosphorylation of P38 MAPK participated in the attenuation of MCAO-induced brain injuries by hypoxic preconditioning of mice

作　　者：蒋淑君[1] 张楠[2] 卜祥宁[2] 刘旭[2] 封素娟[2] 江君[2] 杨巍巍[2] 李俊发[2] 

机构地区：[1]滨州医学院生理学教研室,山东烟台264003 [2]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》2009年第7期691-696,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30670782);国家重点基础性研究项目(2006CB5041);北京市自然科学基金(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(京教人[2008]17号);北京市新世纪百千万人才工程培养经费资助(08-016)

摘　　要：目的探讨P38丝裂原激活蛋白激酶(P38 MAPK)磷酸化和蛋白表达水平在低氧预适应(HPC)降低脑中动脉阻塞(MCAO)所致缺血性脑损伤中的变化。方法利用已建小鼠HPC-MCAO模型,将健康雄性BALB/c小鼠随机分为常氧假手术(H0 Sham)、HPC假手术(H4 Sham)、常氧缺血(H0)和HPC缺血(H4)4组,应用2,3,5-氯化三苯基四氮唑(TTC)染色、N issl染色等方法观察脑损伤情况,应用W estern b lot并结合Gel Doc凝胶成像系统,定量检测小鼠脑组织内P38 MAPK磷酸化和蛋白表达水平的变化。结果HPC可明显减小MCAO所致的脑梗死体积(P<0.05)。与H0 sham相比,缺血组小鼠皮层缺血核心区和半影区P38 MAPK磷酸化水平显著升高(P<0.05,n=6),HPC可进一步增加缺血半影区和对侧皮层组织中P38 MAPK磷酸化水平(P<0.05,n=6)。各组间P38MAPK蛋白表达量水平无明显变化。结论P38 MAPK可能参与了HPC降低MCAO所致小鼠缺血性脑损伤的作用。Objective To explore the effect of hypoxic preconditioning （HPC） on middle cerebral artery occlusion （MCAO）-induced brain injury of mice and the changes of P38 mitogen activated protein kinase （P38 MAPK） phosphorylation and protein expression levels in the ischemie cortex. Methods Using HPC and MCA0 mouse models, healthy male BALB/c mice were randomly divided into 4 groups ： H0 sham, H4 sham, H0 and H4 group.The brain infarct volume and neural injury were determined by 2,3,5-Triphenyhetrazolium chloride （TI＇C） and Nissl staining . Western blot combined with Gel Doe imaging systems was applied to examine the changes of P38 MAPK phosphorylation and protein expression in murine brain. Results HPC significantly attenuate the brain injury induced by MCAO （P 〈 0. 05 ）. Phosphorylation level of P38 MAPK in the ischemic core and penumbra increased significantly as compared with H0 sham group （P 〈 0. 05, n = 6 for each group）. HPC increased the phosphorylation levels of P38 MAPK in the penumbra and contralateral cortex （P 〈0. 05, n =6）. However, there was no significant change in P38 MAPK protein expression. Conclusion P38 MAPK might be involved in the attenuation of MCAO-induced brain injury by HPC.

关 键 词：脑低氧预适应 脑中动脉梗塞 P38丝裂原激活蛋白激酶 磷酸化水平 蛋白表达量 

分 类 号：R743[医药卫生—神经病学与精神病学]