二苯乙烯苷对东莨菪碱致小鼠学习记忆障碍的改善作用

背景中药何首乌能够提高小鼠学习记忆和抗脑缺血能力,而二苯乙烯苷是何首乌的主要有效成份,具有较强的抗氧化与延缓衰老等脑保护作用.目的观察由东莨菪碱所致学习记忆障碍的小鼠给予二苯乙烯苷后,其学习记忆障碍的改善.设计随机对照实验.单位首都医科大学宣武医院药理研究室.材料实验于2000-02/05在首都医科大学宣武医院药物研究中心完成.选取雄性昆明小鼠50只,随机分为5组即正常组、模型组、阳性对照组、二苯乙烯苷0.03g/kg组、二苯乙烯苷0.1g/kg组.二苯乙烯苷为首都医科大学宣武医院药理室从中药何首乌中提取的有效成分,阳性对照药为吡拉西坦,Morris水迷宫和避暗反射箱由中国医学科学院药物研究所研制.方法实验前5d开始给药,正常组及模型组分别给予自来水灌胃,阳性对照组给予吡拉西坦0.7 g/(kg·d),二苯乙烯苷0.03 g/kg组给予二苯乙烯苷0.03 g/(kg·d),二苯乙烯苷0.1 g/kg组给予二苯乙烯苷0.1g/(kg·d),连续5 d.第6天各组灌胃给药30 min后开始造模(正常组腹腔注射等量生理盐水,其余各组均腹腔注射东莨菪碱1 mg/kg),20 min后进行Morris水迷宫和避暗测试.Morris水迷宫造模注射剂量为1 mg/kg,避暗测试造模注射剂量为10 mg/kg.主要观察指标①各组小鼠在Morris水迷宫中的搜索距离和时间.②各组小鼠在避暗实验中的潜伏期和电击次数.结果实验纳入50只小鼠,49只进入结果分析,模型组腹腔注射东莨菪碱时因腹腔出血死亡1只.①Morris水迷宫测试结果二苯乙烯苷0.1 g/kg组小鼠搜索时间及搜索距离较模型组均显著缩短(77.814±46.492),(99.319±38.104)s;(1370.914±917.40),(1 808.77±869.36)cm;P均＜0.05].②避暗反应测试结果二苯乙烯苷0.03 g/kg与0.1g/kg组小鼠的电击次数较模型组均明显减少(0.00±0.00),(0.00±0.00),(0.8571±2.267)次,P＜0.01],且潜伏期有延长的趋势(300±0.00),(300±0.00),(269.71±80.128)S].结论对东莨菪碱所致学习记忆障碍模型小鼠,给予二苯乙烯苷后可缩短其在Morris水迷宫中的搜索时间和搜索距离,减少避暗的错误次数,对学习记忆障碍有一定的改善作用.

Ameliorative effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on learning and memory disorder induced by scopolamine in mice

BACKGROUND: Chinese herb tuber fleeceflower root can enhance learning and memory ability and anti-cerebral ischemia ability in rats,while 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside,the main effective component of tuber fleeceflower root,has very strong brain-protecting ef fects such as anti-oxidation and anti-aging.OBJECTIVE: To observe the amelioration of learning and memory dis order after administration of 2,3,5,4'-tetrahydroxystilbene-2-O-3-D-glucoside in mice with learning and memory disorder caused by scopolamine.DESIGN: Randomized controlled trial.SETTING: Institute of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.MATERIALS: The experiment was conducted in the Institute of Pharmacology,Xuanwu Hospital of Capital University of Medical Sciences,be tween February 2000 and May 2000.Totally 50 male Kunming mice were recruited and randomized into 5 groups: normal control group, model group,positive control group, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside 0.03 g/kg group (low-dose group), and 2,3,5,4 '-tetrahydroxystilbene-2-O-β- D-glucoside 0.1 g/kg group(high-dose group).2,3,5,4'-tetrahydroxystil bene-2-O-β-D-glucoside was an effective component extracted from Chinese herb tuber fleeceflower root in the Department of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.Piracetam was the positive control drug.Morris water maze and passive avoidance reflex box were made in the Institute of Materia Medica, the Chinese Academy of Medical Sciences.METHODS:Administration was given 5 days before experiment.Tap water was intragastrically grven into the mice in normal group and model group. Piracetam of 0.7 g/(kg.d) was given to the mice in positive control group and 0.03 g/kg of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside was given to small-dose group and 0.1 g/kg to large-dose group for 5 consecutive days.Model establishment started 30 minutes after adminis tration in each group on day 6. The same volume of normal saline was in traperitoneally injected into the mice in normal control group and 1 mg/kg of scopolamine was intraperitoneally injected into mice in the other groups.Morris water maze and passive avoidance tests were carried out 20 minters later.Injection dose of model establishment of Morris water maze was 1 mg/kg and that of passive avoidance test was 10 mg/kg.MAIN OUTCOME MEASURES:① Searching distance and time of mice in Morris water maze in each group.② Latency and entry-times of mice in passive avoidance test in each group.RESULTS:All the 50 mice were recruited in the experiment,and 49 of them entered the result analysis,1 mouse in model group died because of intraperitoneal hemorrhage when scopolamine was injected.① Results of Morris water maze test: Searching time and distance were significantly shortened in large-dose group as compared to those in model group(77.814± 46.492), (99.319± 38.104)s; (1 370.914± 917.40), (1 808.77± 869.36)cm; P all ＜ 0.05]. ② Results of passive avoidance test: The number of en try times in small-dose group and large-dose group was significantly de creased compared with that in model group (0.00± 0.00), (0.00± 0.00),(0.8571± 2.267) times, P ＜ 0.01], and the latency had an extended tenden cy (300± 0.00), (300± 0.00), (269.71± 80.128) s ].CONCLUSION: 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside given to mice with learning and memory disorder induced by scopolamine can shorten the searching time and distance in Morris water maze and reduce the number of mistake-making times in passive avoidance test. It suggests that it has ameliorative effects on learning and memory disorder.