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何首乌有效成分对D-半乳糖致拟痴呆大鼠脑内胆碱酶和血清β淀粉样蛋白的影响

发表时间:2013-12-15  浏览量:964  下载量:464
全部作者: 李小黎,刘晓梅,赵瑞珍,田青
作者单位: 北京中医药大学第三附属医院脑病科
摘 要: 目的:观察何首乌有效成分二苯乙烯苷(2,3,5,4-tetrahydroxy-stilbene-2-O-β-D-glylcoside,TSG)对D-半乳糖致拟痴呆大鼠学习记忆能力、海马胆碱乙酰转移酶(choline acetyltransferase,ChAT)、乙酰胆碱酯酶(acetylcholinesterase,AChE)活性以及血清粉样蛋白(β-amyloid 1-42, Aβ1-42)含量的影响。方法:雄性Wistar大鼠60只随机分为6组(每组10只),1) 正常对照组;2) 模型组(D-半乳糖致痴呆大鼠);3) 模型+阳性对照药组[盐酸多奈哌齐0.9 mg/(kg·d)];4) 模型+TSG小剂量组[0.05 g/(kg·d)];5) 模型+TSG中剂量组[0.10 g/(kg·d)];6) 模型+TSG大剂量组[0.20 g/(kg·d)]。采用去D-半乳糖的拟阿尔茨海默病(Alzheimer’s disease, AD)大鼠模型,D-半乳糖按300 mg/kg背部皮下注射6周,每日1次。对照组注射等剂量生理盐水,连续6周。同时灌胃给药,每日1次,连续12周。治疗结束后以Morris水迷宫、避暗实验为记忆评价指标,并采用放射免疫分析测定各组大鼠海马ChAT,AChE以及Aβ1-42表达。结果:在Morris实验记忆测试中,拟痴呆大鼠表现出明显的学习记忆障碍,穿越平台次数减少(P<0.05),避暗实验中模型组大鼠入暗箱的潜伏期缩短(P<0.01),5 min进入暗箱遭电击的次数明显增加(P<0.05),海马AChE活性增高(P<0.01),而ChAT的活性降低(P<0.01),血清中Aβ1-42增加(P<0.01);与模型组比较,TSG组穿越平台次数较模型组显著增加(P<0.05),避暗潜伏期延长,遭电击次数减少(P<0.05);海马AChE活性降低(P<0.05,P<0.01),而ChAT的活性升高(P<0.05,P<0.01),血清中Aβ1-42降低(P<0.01),以TSG中剂量作用较为显著。结论:TSG能明显改善拟痴呆大鼠的学习记忆能力,具有抑制乙酰胆碱降解、促进其合成、且减少或抑制Aβ过度产生的作用。
关 键 词: 中药药理学;痴呆;二苯乙烯苷;胆碱乙酰转移酶;乙酰胆碱酯酶;淀粉样β蛋白
Title: Influence of effective components on activities of cholinesterase and levelof β-amyloid protein in serum of rats with dementia induced by D-galactose
Author: LI Xiaoli, LIU Xiaomei, ZHAO Ruizhen, TIAN Qing
Organization: Department of Encephalopathy of the Third Affiliated Hospital, Beijing University of Chinese Medicine
Abstract: Objective: To study the effects of 2,3,5,4-tetrahydroxy-stilbene-2-O-β-D-glylcoside(TSG)on learning and memory abilities, activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus and content of β-amyloid 1-42 (Aβ1-42) in serum of rats mice with dementia induced by D-galactose. Methods: 60 male Wistar rats were randomly divided into 6 groups (n=10), 1) normal control group; 2) model group (D-galactose dementia rats); 3) model+positive control drug groupfor [HCl donepezil donepezil 0.9 mg/(kg·d)]; 4) model+TSG small dose group [0.05 g/(kg·d)]; 5) model+TSG middle dose group [0.10 g/(kg·d)]; 6) model+TSG big dose group [0.20 g/(kg·d)]. Alzheimer’s disease (AD) rat models were made by injecting subcutaneously D-galactose at a dosage at 300 mg/kg for 6 weeks, control group were injected with saline. Drugs were simultaneously administered orally once daily for 12 weeks. At the end of treatment, the Morris water maze, passive avoidance test for memory were taken, and activities of ChAT and AChE in hippocampus, content of Aβ1-42 were determined with radioimmunoassay. Results: In Morris memory test, model rats showed a significant learning and memory obstacles in swimming cross the platform (P<0.05). In passive avoidance test, incubation period of model rats walked into the black box were shortened (P<0.01), times of electric shocks increased significantly in 5 min (P<0.05), activity of AChE in hippocampus increased(P<0.01), while the activity of ChAT decreased (P<0.01), and level of Aβ1-42 in serum increased (P<0.01). Compared with the model group, times of TSG group swam across the platform significantly increased (P<0.05), passive avoidance latency decreased (P<0.05), the number of electric shocks reduced. Activity of AChE in hippocampus decreased (P<0.05, P<0.01), while the activity of ChAT increased (P<0.05, P<0.01), level of Aβ1-42 in serum decreased (P<0.01). Effects of TSG at moderate doses was more significant. Conclusion: TSG can significantly improve learning and memory in rats with dementia, inhibit the degradation of acetylcholine and promote its synthesis, and can reduce or inhibit overproduction of Aβ.
Key words: pharmacology of traditional Chinese medicine; dementia; 2,3,5,4- tetrahydroxy-stilbene-2-O-β-D-glylcoside; choline acetyl transferase; acetylcholinesterase; β-amyloid protein
发表期数: 2013年12月第23期
引用格式: 李小黎,刘晓梅,赵瑞珍,等. 何首乌有效成分对D-半乳糖致拟痴呆大鼠脑内胆碱酶和血清β淀粉样蛋白的影响[J]. 中国科技论文在线精品论文,2013,6(23):2270-2274.
 
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