蛋白激酶CβⅡ和γ参与低氧预适应降低脑中动脉阻塞所致鼠脑缺血性损伤  

cPKCβⅡ and γ participated in the attenuation of MCAO-induced brain injuries of mice following hypoxic preconditioning

作　　者：杨巍巍[1] 江君[1] 卜祥宁[1] 张楠[1] 谢培伦[1,2] 张伯民[1,2] 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 [2]北京市科协

出　　处：《基础医学与临床》2009年第2期129-134,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30670782;30871219);国家"973"计划(2006CB5041);北京市自基金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(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：目的探讨低氧预适应（HPC）对脑中动脉梗塞（MCAO）小鼠脑的保护作用,以及缺血皮层内经典型蛋白激酶C（cPKC）βⅡ和γ膜转位水平的改变。方法健康雄性BALB/c小鼠（18-22 g,8-10周）随机分为：H0假手术（n=6）,H0缺血（n=6）,H4假手术（n=6）和H4缺血（n=6）组。运用整体低氧预适应模型和脑中动脉梗塞缺血模型,结合2,3,5氯-化三苯基四氮唑（TTC）染色、SDS聚-丙烯酰胺凝胶电泳（SDS-PAGE）和蛋白印迹（W estern blot）等分子生物学技术,观察脑梗死面积、缺血区密度值和水肿率,以及MCAO小鼠缺血皮层组织内PKCβⅡ和γ膜转位水平的变化。结果研究发现,HPC可明显减小MCAO导致的鼠脑梗死面积（P〈0.05）,降低缺血区吸光度值（P〈0.05）和水肿率（P〈0.05）;与H0假手术组相比,缺血组小鼠皮层半影区cPKCβⅡ和γ膜转位水平显著降低（P〈0.05）;与H0缺血组小鼠皮层半影区相比,H4缺血组小鼠皮层半影区内PKCβⅡ和γ膜转位水平明显增高（P〈0.05）。结论HPC可能通过增加MCAO小鼠皮层组织内cPKCβⅡ和γ的膜转位水平,对缺血损伤起保护作用。Objective To explore the protection of hypoxic preconditioning （HPC） on middle cerebral artery occlusion （MCAO）-induced brain injuries of mice and the changes in protein kinase C （PKC） βⅡ and γ membrane translocation in ischemic cortex of MCAO mice. Methods Male BALB/c mice （18 - 22 g, 8 -10 w） were randomly divided to H0 ＋ Sham （ n = 6 ）, H0 ＋ Isehemia （ n = 6 ）, H4 ＋ Sham （ n = 6 ） and H4 ＋ Ischemia （ n = 6 ） group. Using our unique hypoxic preconditioned mouse model and middle cerebral artery occlusion mouse model, combined with TTC staining, SDS-PAGE and Western blot, we observed the changes in infarction sizes, density, edema ratio, and changes in cPKCβⅡ and γ membrane translocation in ischemic cortex of MCAO mice. Results HPC significantly reduced infarction size （ P 〈 0. 05 ）, density of infarct area （ P 〈 0. 05 ） and edema ratio （ P 〈 0. 05 ）. As compared with H0 ＋ sham group, cPKCβⅡ and γ membrane translocation levels in penumbra of ischemic cortex decreased significantly （ P 〈 0. 05 ）. Whereas cPK CβⅡ and γ membrane translocation levels in penumbra of ischemic cortex in H4 ＋ Isehemia group increased significantly compared with that of mice in H0 ＋ Isehemia group （ P 〈 0. 05）. Conclusion Hypoxic preconditioning increased levels of cPKCβⅡ and γ membrane translocation in penumbra of middle cerebral artery occluded mice, which may be involved in the protective effect of HPC to severe ischemic injury.

关 键 词：脑中动脉梗塞 低氧预适应 蛋白激酶C 膜转位 

分 类 号：R743[医药卫生—神经病学与精神病学]