低氧预适应减轻脑中动脉阻塞所致小鼠缺血性脑损伤  

Hypoxic preconditioning attenuated MCAO-induced brain ischemic injuries of mice

作　　者：江君[1] 杨巍巍[1] 张楠[1] 卜祥宁[1] 郭梦语[1,2] 赵欣怡[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113-118,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30670782;30871219);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：目的探讨低氧预适应(HPC)对脑中动脉阻塞(MCAO)所致脑缺血性损伤的影响及其可能机制。方法借助已建小鼠整体HPC和脑MCAO模型,应用2,3,5氯-化三苯基四氮唑(TTC)染色、神经行为学评分、SDS-PAGE和W estern b lot等技术方法,观察脑梗死面积、水肿率、行为学,以及脑梗死核心和半影区新奇型蛋白激酶C(nPKC)膜转位的变化。结果MCAO可诱发小鼠脑皮层、海马和丘脑(由于发生率很低,数据未统计)等3种典型缺血模式;在皮层缺血模式中,HPC明显减小脑梗死面积(P<0.05,n=12)、缺血区吸光度值(P<0.05,n=12)和水肿率(P<0.05,n=12);而在海马缺血模式上,HPC只明显降低海马梗死区吸光度值(P<0.05,n=12);HPC可在一定程度上缓解MCAO小鼠的行为学改变;此外,HPC可缓解MCAO所致皮层缺血半影区nPKC膜转位水平的降低。结论HPC降低MCAO所致脑缺血性损伤,且nPKC可能参与了这种保护作用。ObjectiveTo explore the effects of hypoxic preconditioning （HPC） on middle cerebral artery occlusion （MCAO） -induced brain injuries and its possible mechanisms. Methods Using our established HPC and MCAO mouse models, and the techniques of 2,3,5-Triphenyhetrazolium chloride （ TTC ） staining, neurological evaluation, SDS-PAGE and Western blot, we observed the changes in infarction sizes, edema ratio, behavior score, and nPKC membrane translocation in the ischemie core and penumbra of mice following hypoxic exposure and ischemic injuries. Results MCAO could induce three types of cerebral ischemia ： cortical, hippocampal and thalamic ische- mia （data not shown due to the rare incidence） ; In the cortical ischemia, HPC significantly reduced infarction size （P 〈0. 05, n = 10）, density of infarct area （P 〈0. 05, n = 10） and edema ratio （P 〈0. 05, n =6） ; However, HPC only decreased the density of infarct area significantly （ P 〈 0.05, n = 7） in the hippocampal ischemia; HPC also partially relieved the MCAO - induced neurological deficits of mice ; In addition , HPC could prevent the decreased nPKC membrane translocation induced by MCAO in penumbra of mic＇e brain. Conclusion HPC can attenuate MCAO-induced brain injuries, and nPKC may be involved in the neuroprotection.

关 键 词：低氧预适应 脑中动脉阻塞 TTC染色 缺血半影区 nPKC 

分 类 号：R743[医药卫生—神经病学与精神病学]