多奈哌齐对血管性痴呆大鼠室管膜下区神经发生相关因子VEGF和IGF-1的影响  

The effect of donepezil in neurogenetic factors VEGF and IGF-1 within the subventricular zone of rats after vascular dementia

作　　者：满江 王建平[1] 崔可飞[2] 付晓杰 张帝[1] 鲁争芳 高宇峰 MAN Jiang;WANG Jianping;CUI Kefei(Department of Neurology,The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第五附属医院神经内科,河南郑州450052 [2]郑州大学第一附属医院超声科,河南郑州450052 [3]郑州大学第一附属医院神经介入科,河南郑州450052

出　　处：《中风与神经疾病杂志》2018年第10期900-903,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(No.81571137;No.81771247);河南省医学科技攻关计划项目(No.201501005)

摘　　要：目的探讨多奈哌齐(胆碱酯酶抑制剂)对血管性痴呆(vascular dementia,VD)大鼠室管膜下区(subventricular zone,SVZ)神经发生相关因子血管内皮生长因子(vascular endothelial growth factor,VEGF)及胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的影响。方法将雄性大鼠按随机数字表法分为假手术+溶剂组、2VO+溶剂组、2VO+多奈哌齐组3组。用永久性结扎大鼠双侧颈总动脉法(two-vessel occlusion,2VO)制造VD模型。用Morris水迷宫系统对各组大鼠进行学习记忆能力行为学测试。采用5-溴-2-脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,Brd U)标记增殖细胞,Nestin标记神经干细胞,免疫荧光观察各组大鼠SVZ内nestin+/Brd U+细胞的数量。Western blot分析各组大鼠SVZ中VEGF和IGF-1蛋白表达量的变化。结果 2VO+溶剂组大鼠水迷宫表现明显比另两组差,差异有统计学意义(P <0. 05)。术后15 d,2VO+多奈哌齐组大鼠SVZ中nestin+/Brd U+细胞数,及VEGF和IGF-1蛋白表达量较2VO+溶剂组显著增多(P <0. 05)。结论我们认为多奈哌齐对VD大鼠SVZ神经发生相关因子VEGF和IGF-1表达量有显著上调作用,并部分通过提高VEGF和IGF-1表达量促进VD后SVZ神经发生。Objective To investigate the effect of donepezil(an acetylcholinesterase inhibitor)in neurogenetic factors vascular endothelial growth factor(VEGF)and insulin-like growth factor-1(IGF-1)in the subventricular zone(SVZ)of rats after vascular dementia(VD).Methods We randomly assigned the rats into three groups:sham-operated rats treated with vehicle(Sham+vehicle),two-vessel occlusion(2VO)-operated rats treated with vehicle(2VO+vehicle),2VO rats treated with donepezil(2VO+DZ).2VO model can be induced by permanently occluding the right and left common carotid arteries in rats.Morris Water Maze test was used to measure spatial memory of rats.We labeled proliferative cells with 5-bromo-2-deoxyuridine(BrdU),and neural stem cells(NSCs)with nestin.The expression of nestin+/BrdU+cells in the SVZ was detected by immunofluorescence.The expression of VEGF and IGF-1 in the SVZ was quantified by Western blot.Results 2VO+DZ group showed better performance in Morris Water Maze test than 2VO+vehicle group(P<0.05).The number of nestin+/BrdU+cells and the expression of VEGF and IGF-1 in rats of 2VO+DZ group were markedly increased compared with those in the 2VO+vehicle group(P<0.05).Conclusion Donepezil can increase the expression of VEGF and IGF-1 in SVZ and may partly promote neurogenesis in SVZ after VD via VEGF and IGF-1.

关 键 词：血管内皮生长因子 胰岛素样生长因子-1 室管膜下区 血管性痴呆 神经发生 

分 类 号：R743[医药卫生—神经病学与精神病学]