促红细胞生成素对血管性痴呆大鼠认知功能及其海马CAl区神经细胞凋亡的影响  

Effect of erythropoietin on cognition and neuron apoptosis in CA1 region of hippocampus in vascular dementia rats

作　　者：黄树其[1] 杨月嫦[1] 黄流清[1] 邵福源[1] 

机构地区：[1]上海长征医院神经内科,200003

出　　处：《中华老年医学杂志》2013年第11期1228-1232,共5页Chinese Journal of Geriatrics

摘　　要：目的探讨促红细胞生成素（EP0）对血管性痴呆（VaD）大鼠认知功能及其海马CAl区神经细胞凋亡的影响。方法将54只Wistar大鼠分为假手术组、VaD组和EPO组，采用永久性结扎双侧颈总动脉的方法建立VaD模型。采用Y一迷宫观察术后4周、8周、12周大鼠的空间学习和记忆能力，应用TUNEL染色检测大鼠海马CAl的神经细胞凋亡数，通过免疫组织化学和逆转录聚合酶链反应检测大鼠海马CAl区Bcl-2和BaxmRNA表达水平的变化。结果与VaD组大鼠比较，术后4周、8周、12周EPO治疗组大鼠迷宫作业错误反应次数明显减少，总反应时间明显缩短（均P〈0．05）；术后4周、8周和12周VaD组大鼠海马CAl区凋亡细胞数目分别为（20．50±3．29）个、（33．58±3．48）个和（54．17±4．26）个，比EPO治疗组的（10．50±2．43）个、（23．92±3．18）个和（36．92土4．10）个多（t=4．23、3．54、5．05，P=0．013、0．024、0．007）；术后4周、8周和12周EP0治疗组Bcl-2阳性细胞数和Bcl-2mRNA表达较VaD组明显增多，Bax阳性细胞数和BaxmRNA表达较VaD组明显减少（均P〈0．05）。结论EPO可能通过调控VaD大鼠海马CAl区Bcl-2和Bax表达抑制神经细胞凋亡，改善其认知功能障碍。Objective To explore the effect of erythropoietin （EPO） on cognition and neuron apoptosis in CA1 region of hippocampus in vascular dementia （VaD） rats. Methods 54 Wistar rats were randomly divided into three groups： sham control group, VaD group, VaD＋ EPO group （n= 18, each）. The bilateral common carotid arteries of Wistar rats were permanently ligated to establish VaD models. Spatial study and memory were observed by Y maze test at 4, 8 and 12 weeks after operation. Neuron apoptosis in CA1 area of hippocampus was measured by terminal deoxynucleotidyl transferase （TdT）-mediated dUTP-biotin nick end labeling （TUNEL） method. The protein and mRNA expressions of Bcl-2 and Bax in CA1 region of hippocampus were detected by immunohistochemistry and RT-PCR at 4, 8, 12 weeks after operation. Results Compared with VaD group, the VaDq EPO group had better performances including less error reaction times and shorter total reaction time in Y-maze （both P〈0.05） at 4, 8, 12 weeks after operation. The apoptotic neuronal cells in CA1 region of hippocampus was decreased in VaD--EPO group than in VaD group at 4, 8, 12 weeks after operation [（10.50±2.43） vs. （20.50±.29）, （23.92±3.18） vs. （33.58±3.48） and （36.92±4.10） vs. （54.17±4.26）, t=4.23, 3.54, 5.05, P=0.013, 0.024, 0.007, respectively. The Bcl-2-positive cells and Bcl-2 mRNA expression were increased, and the Bax- positive cells and Bax mRNA expression were decreased in VaDq-EPO group than in VaD group （all P %0.05）. Conclusions Erythropoietin can improve cognitive function by inhibiting neuron apoptosis through regulation of Bcl-2 and Bax expression in CA1 region of hippoeampus.

关 键 词：痴呆 血管性 红细胞生成素 认知 细胞凋亡 

分 类 号：R965[医药卫生—药理学]