DNA修复酶对大鼠局灶性脑缺血后远隔部位损伤修复的影响  

Influence of apurinic/apyrimidinic endonuclease on repair of rat brain regions distant from the focal cerebral ischemia site

作　　者：黄清[1] 邵艳敏[1] 冯洁[1] 李灵娟[1] 刘运海[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008

出　　处：《中华老年医学杂志》2014年第9期1010-1013,共4页Chinese Journal of Geriatrics

基　　金：湖南省自然科学基金（12JJ5072）;高校青年教师助推专项（2011QNZT149）

摘　　要：目的 观察大鼠大脑中动脉局灶性梗死后远隔部位海马的继发损害导致DNA修复酶（APE）以及DNA氧化损伤指标8-羟基脱氧鸟苷（8-OHdG）的改变. 方法 采用SD大鼠制作改良的大脑中动脉线栓模型,将大鼠分为假手术组和模型组（pMCAO）,术后不同时间点观察脑组织病理变化,免疫组织化学染色检测APE、8-OHdG的表达变化,TUNEL染色检测细胞凋亡. 结果 缺血侧海马CA1区APE的表达自缺血2h开始下降,并随缺血时程延长持续下降（F=11.91,P＜0.05）;8OHdG和TUNEL阳性表达自缺血6h开始出现,随缺血时程延长,两者阳性表达持续增加（F=9.23、10.46,均P＜0.05）,缺血24～72 h基本维持在同一水平;与假手术组比较,pMCAO组大鼠APE、8-OHdG和TUNEL阳性表达差异均有统计学意义（均P＜0.05）. 结论 大鼠大脑中动脉局灶性脑缺血后海马部位存在DNA氧化损伤;局灶性脑缺血后远隔部位APE表达下降,DNA氧化损伤积累和发展诱导细胞凋亡.Objective To investigate changes in the expression of apurinic/apyrimidinic endonuclease （APE） and the oxidative DNA damage marker 8 OHdG in distant hippocampus regions of the rat brain after focal cerebral ischemia of the middle cerebral artery.Methods SD rats were divided into the sham surgery group and the pMCAO group （induced by middle cerebral artery occlusion）.Pathological changes in brain tissues were examined at 2 h,6 h,12 h,24 h,48 h and 72 h.The expression of APE and 8-OHdG was measured by immunohistochemical staining methods.TUNEL staining was performed to detect apoptosis.Results Reduction of APE expression in the CA1 region of the hippocampus on the ischemia side appeared at 2 h in the pMCAO group and continued as ischemia persisted （F=11.91,P＜0.05）.The expression of 8OHdG and TUNEL immunoreactivity in the CA1 region of the hippocampus on the ischemia side were first observed at 6h in the pMCAO group and intensified during the remainder of induced ischemia （F=9.23 and 10.46 respectively,P＜0.05 for both）.Compared with the sham group,8-OHdG expression and TUNEL immunoreactivity in the pMCAO group were at nearly the same levels from 24 h to 72h.Conclusions Oxidative DNA damage occurs in hippocampus regions of the rat brain after experimentally induced focal cerebral ischemia of the middle cerebral artery.APE expression declines in regions distant from focal cerebral ischemia.Development and accumulation of oxidative DNA damage can induce apoptosis in certain brain regions.

关 键 词：脑缺血 DNA修复酶类 细胞凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]