姜黄素通过抗应激作用改善脑缺血再灌注大鼠工作记忆

目的：探讨姜黄素预先给药对大鼠全脑缺血再灌注后空间工作记忆改善作用的机制.方法：成年雄性SD大鼠120只,经T迷宫训练后按随机数字表法分成5组：假手术组（SHAM组）、脑缺血再灌注组（IR组）、姜黄素组（CUR组）、皮质酮组（CORT组）和姜黄素＋皮质酮组（CUR＋ CORT组）,每组24只.各组给予相应药物、溶媒注射,1h后全脑缺血10 min后再灌注,于再灌注7d行T迷宫检测工作记忆,于再灌注2h、1、3、7d采血清和脑组织标本,TUNEL法检测海马CA1区神经元凋亡情况,ELISA检测血清皮质酮（CORT）和海马脑源性神经营养因子（BDNF）的表达.结果：与SHAM组比较,IR组CORT水平增加（164±36 vs 92±24,P＜0.05）,海马BDNF含量降低（8.7±2.8 vs 19.4±5.1,P＜0.05）,海马CA1区凋亡神经元数目增加（233±22 vs 21±4,P＜0.01）,T迷宫正确率降低（65％±7％ vs 87％±9％,P＜0.05）;与IR组比较,CUR组CORT水平降低（102±18,P＜0.05）,海马BDNF含量增加（13.3±3.3,P＜0.05）,海马CA1区凋亡神经元数目减少（163±11,P＜0.05）,T迷宫正确率增高（79％±10％,P＜0.05）;与IR组比较,CORT组海马BDNF降低（4.4±1.2,P＜0.05）,海马CA1区凋亡神经元数目增加（332±35,P＜0.05）,T迷宫正确率降低（58％±6％,P＜0.05）;与CORT组比较,CUR＋ CORT组海马BDNF含量增加（10.5±2.3,P＜0.05）,海马CA1区凋亡神经元数目降低（211±27,P＜0.05）,T迷宫正确率增高（71％±12％,P＜0.05）.结论：姜黄素预先给药可通过抑制应激反应改善大鼠全脑缺血再灌注后空间工作记忆.

Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting the stress response

AIM：To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism.METHODS：After trained on a modified T-maze,120 adult SD rats were randomly divided into 5 groups：SHAM group,cerebral ischemia-reperfusion group （IR group）,Curcumin group （CUR group）,corticosterone group （CORT group） and Curcumin ＋ CORT group （CUR＋CORT group）.Rats were treated with drugs or vehicles 1 h before 10min global cerebral ischemia.Six rats in each group 7 days after reperfusion were tested in T-maze.Six rats in each group were sacrificed at 2 h,1,3 and 7d after reperfusion and their serum or brains were harvested.TUNEL assays were performed using the in situ cell death detection kit to detect the apoptosis neurons of CA1 area.Levels of serum corticosterone and hippocampi brain-derived neurotrophic factor （BDNF） was detected using ELISA procedure.RESULTS：Compared with SHAM group,corticosterone levels in IR group was increased （164 ± 36 vs 92 ± 24,P〈0.05）,and BDNF in hippocampiwas decreased （8.7 ± 2.8 vs 19.4±5.1,P〈0.05）,apoptotic neurons in CA1 areas was increased （233±22 vs 21±4,P〈0.01）,and percentage of T-maze correct responses was decreased （65% ± 7% vs 87% ± 9%,P〈0.05）.Compared with IR group,serum corticosterone levels in CUR group was decreased （102±18,P〈0.05）,BDNF in hippocampi was increased （13.3 ± 3.3,P 〈 0.05）,apoptotic neurons in CA1 areas was decreased （163±11,P〈0.05）,and percentage of T-maze correct responses was increased （79 % ±10 %,P 〈 0.05）.Compared with IR group,CORT group hippocampi BDNF levels was decreased （4.4± 1.2,P〈0.05）,apoptotic neurons in CA1 areas was increased（332± 35,P〈0.05）,and percentage of T-maze correct responses was decreased （58% ± 6%,P〈 0.05）.Compared with CORT group,hippocampi BDNF levels in CUR＋ CORT group was increased （10.5 ± 2.3,P〈0.05）,apoptotic neurons in CA1 areas