消旋丁苯酞对慢性脑缺血大鼠认知功能的影响及其生化机制研究  

Protective effects of 3-n-butylphthalide on the cognitive dysfunction of chronic cerebral ischemic rats and its biochemical mechanisms

作　　者：赵万红[1] 罗超[1] 龚应霞[1] 张正洪[1] 潘龙瑞[1] 姚柏春[1] 

机构地区：[1]湖北医药学院基础医学院,十堰市442000

出　　处：《中华老年医学杂志》2014年第4期412-415,共4页Chinese Journal of Geriatrics

基　　金：湖北省教育厅重点项目（D20102101）;湖北医药学院优秀中青年科技创新团队项目（2011CXG03）

摘　　要：目的观察消旋丁苯酞（dl—NBP）对慢性脑缺血大鼠认知的改善作用，并研究其生化机制。方法永久性结扎老龄大鼠（15月龄）双侧颈总动脉3个月，制备脑缺血模型。将大鼠分为四组：假手术组、模型组、NBP30和120mg／kg。前两组灌胃给予植物油，后两组给予NBP，45d后，用Morris水迷宫检测大鼠的空间认知能力。同时，取皮层和海马，用生化法检测超氧化物歧化酶（s0D）、胆碱乙酰基转移酶（ChAT）和真性胆碱酯酶（TChE）活力以及丙二醛含量。结果Morris水迷宫实验5天训练中，模型组逃避潜伏期变化很小，NBP小剂量组从（57．7±3．8）S缩短至（30．5±17．1）s，大剂量组从（58．4±1．8）S缩短至（28．9±11．3）S，与模型组比较差异有统计学意义（P〈0．05或P〈0．01）。空间探索实验中，与模型组比较，NBP小剂量和大剂量组目标象限活动时间百分比明显增加，分别为（26．0±6．9）％和（27．3±5．3）％（P〈0．05）。模型组皮层SOD升至（134．5±13．9）U／mg，NBP大剂量组降低为（112．3±7．5）U／mg（P〈O．01）。与模型组比较，NBP小、大剂量皮层丙二醛减少，分别为（2．39±0．31）nmol／mg和（1．56±0．19）nmol／mg（P〈0．01）。与模型组比较，NBP小、大剂量组海马丙二醛也减少，分别为（0．71±0．10）nmol／mg和（0．83±0．05）nmol／mg（P〈0．01）。与模型组比较，NBP大剂量组皮层ChAT水平升高，为（1615±100）U／g（P〈0．05）。与模型组比较，NBP小、大剂量海马ChAT水平也升高，分别为（1745±204）和（1697±117）U／g（P〈0．05）。结论NBP通过减轻氧化应激损伤及增强胆碱能神经元的活性机理发挥改善慢性脑缺血大鼠空间认知缺陷的作用。Objective To investigate the protective effects of 3-n-butylphthalide （dl-NBP） on the cognitive dysfunction of chronic cerebral ischemic rats and its mechanism. Methods Old chronic cerebral ischemic rats （15 months） were modelized with ligating bilateral common carotid arteries for three months. Model rats were divided into four groups： sham, model, NBP 30 and 120 mg . kg-1 groups. The former and the latter two groups were administered vegetable oil and NBP for 45 days, respectively. Then, the cognitive function was measured in rats with Morris water maze. Meanwhile, the activities of superoxide dismutase （SOD）, choline acetyltransferase （CHAT） , true choline esterase （TChE）, and the malondialdehyde （MDA） levels in brain cortex and hippocampus were detected with biochemical methods. Results During the five days of Morris water maze, the change of escape latency was from （57.7±3.8） s to （30.5±17.1） s in low dose of NBP group , and from （58.4±1.8） s to （28.9±11.3） s in high dose of NBP group as compared with no change from 60s to 60s in model group. Significant differences were found in escape latency between NBP＇s and model groups（ P〈0. 05 or 0.01）. In spatial exploratory test, the time percentages spent in the platform- quadrant were increased obviously in low and high doses of NBP [（26. 0±6. 9） % and （27.3±5.3） %,respectively, P〈0.05], compared with that of model group. The SOD activity was obviously reduced in cortices of high dose of NBP group [（112.3 ± 7.6） U/mg protein] compared with that （134. 6 ±13.9） U/mg protein of model group （P〈0.01）. The MDA contents were significantly reduced in cortices of low and high, doses of NBP （2. 39±0. 31） nmol/mg protein and （1.56±0.19） nmo[/mg protein, compared with that of model group （P〈0.01）. The MDA contents in hippocampi of low and high doses of NBP （（0.71±0.10） nmol/mg protein and （0.83±0.05） nmol/mg protein] were also decreased significantly , compared with t

关 键 词：认知 氧化性应激 胆碱能纤维 脑缺血 

分 类 号：R965[医药卫生—药理学]