醒脑益智组分中药对AD模型大鼠学习记忆障碍的实验研究
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摘要
目的:观察醒脑益智组分中药对阿尔茨海默病模型大鼠学习记忆功能障碍的影响。方法:分别采用D-gal腹腔注射、Aβ1-40海马内注射以及二者复合造模的方法建立AD动物模型,以Morris水迷宫法筛选适宜动物模型; Wister大鼠随机分为假手术组、AD模型组、石杉碱甲0. 05 mg/kg组、醒脑益智组分中药179. 2mg/kg、89. 6 mg/kg、44. 8 mg/kg组,造模后连续给药30d进行行为学测试,记录Morris水迷宫实验中各组动物的逃避潜伏期、穿台次数、寻找平台的总路程及穿越平台象限路程;采用回避性条件反射-避暗实验观察各组大鼠的逃避潜伏期和记忆错误次数。结果:不同模型组大鼠水迷宫实验显示逃避潜伏期较造模前显著延长,穿台次数也较造模前减少,以复合造模组较为显著;定向航行实验中,各给药组大鼠较复合模型组逃避潜伏期降低,空间探索实验中,各给药组大鼠穿台次数较模型组增加,穿越第四象限的路程百分比也均有提高,以石杉碱甲0. 05 mg/kg组和醒脑益智组分中药179. 2mg/kg组作用较显著;避暗实验中,复合模型组大鼠造模后记忆潜伏时间缩短,且记忆错误次数增加;与复合模型组相比,石杉碱甲组和醒脑益智组分中药高剂量组大鼠记忆潜伏时间延长,记忆错误次数显著降低。结论:醒脑益智组分中药对复合造模致AD模型大鼠学习记忆障碍具有一定改善作用,且呈现剂量依赖性。
Objective: To investigate the effect of Xingnao Yizhi Multi-component Chinese Medicine Group on learning and memory impairment of Alzheimer's Disease(AD) model rats. Methods: Using D-galactose intraperitoneal injection,Aβ1-40 intrahippocampal injection respectively and both recombination to generate the models,and the water maze test to evaluate the learning and memory ability of the rats,then determined the optimized AD model. Wistar rats were randomly divided into sham operation group,AD model group,huperzine group 0. 05 mg/kg,Xingnao Yizhi Multi-component Chinese Medicine Group 179. 2 mg/kg、89. 6 mg/kg and 44. 8 mg/kg. All the rats in each group were given learning and memory praxiology test after continuously intragastric administration for 30 days,the escape latency periods,the number of cross-platform,the cross-platform total distance and platform quadrant distance were recorded in water maze test and the escape latency periods and the error times in step-through test to observe the effects of the drug. Results: the escape latency periods of rats in each model group was increased and the number of cross-platform reduced obviously,the D-galactose intraperitoneal injection combined Aβ1-40 intrahippocampal injection recombination is better than the other two models(P < 0. 05). Compared with model control group,the escape latency periods of rats in each drug group declined,especially the huperzine group 0. 05 mg/kg and Xingnao Yizhi Multi-component Chinese Medicine Group 179.2 mg/kg(P < 0. 05) in place navigation experiment,the number of cross-platform increased,the percentage of journey through the fourth quadrant is also improved obviously in huperzine group 0. 05 mg/kg,Xingnao Yizhi Multi-component Chinese Medicine Group 179. 2 mg/kg、89. 6 mg/kg(P < 0. 05) in space exploration experiment. Conclusion: Xingnao Yizhi Multi-component Chinese Medicine Group provided obvious effect on improving the dysfunction of learning and memory of the combined AD model rats and showed dose-dependent.
Objective: To investigate the effect of Xingnao Yizhi Multi-component Chinese Medicine Group on learning and memory impairment of Alzheimer's Disease(AD) model rats. Methods: Using D-galactose intraperitoneal injection,Aβ1-40 intrahippocampal injection respectively and both recombination to generate the models,and the water maze test to evaluate the learning and memory ability of the rats,then determined the optimized AD model. Wistar rats were randomly divided into sham operation group,AD model group,huperzine group 0. 05 mg/kg,Xingnao Yizhi Multi-component Chinese Medicine Group 179. 2 mg/kg、89. 6 mg/kg and 44. 8 mg/kg. All the rats in each group were given learning and memory praxiology test after continuously intragastric administration for 30 days,the escape latency periods,the number of cross-platform,the cross-platform total distance and platform quadrant distance were recorded in water maze test and the escape latency periods and the error times in step-through test to observe the effects of the drug. Results: the escape latency periods of rats in each model group was increased and the number of cross-platform reduced obviously,the D-galactose intraperitoneal injection combined Aβ1-40 intrahippocampal injection recombination is better than the other two models(P < 0. 05). Compared with model control group,the escape latency periods of rats in each drug group declined,especially the huperzine group 0. 05 mg/kg and Xingnao Yizhi Multi-component Chinese Medicine Group 179.2 mg/kg(P < 0. 05) in place navigation experiment,the number of cross-platform increased,the percentage of journey through the fourth quadrant is also improved obviously in huperzine group 0. 05 mg/kg,Xingnao Yizhi Multi-component Chinese Medicine Group 179. 2 mg/kg、89. 6 mg/kg(P < 0. 05) in space exploration experiment. Conclusion: Xingnao Yizhi Multi-component Chinese Medicine Group provided obvious effect on improving the dysfunction of learning and memory of the combined AD model rats and showed dose-dependent.
引文
1龙定超,李定君.中枢胆碱能神经系统研究相关进展.中国医药指南,2012; 10(7)∶70~72
2 郭力军,计德利,孙计桃,等.淫羊藿苷对AD模型大鼠神经元超微结构的影响.内蒙古医学杂志,2015; 47(6)∶657~660
3 周娇娇,阙建宇,于雯雯,等. Morris水迷宫检测动物学习记忆水平的方法学.中国老年学杂志,2017; 37(24)∶6274~6277
4 廖艺聪,李艳,王雷,等.小鼠避暗实验三种训练方法的效果比较.井冈山大学学报(自然科学版),2011; 32(04)∶101~103
5 Sasaki K,Han J,Shimozono H,et al. Caffeoylquinic acidrich purple sweet potato extract,with or without anthocyanin,imparts neuroprotection and contributes to the improvement of spatial learning and memory of SAMP8Mouse. J Agric Food Chem,2013; 61(21)∶5037~5045
6 侯林,李万忠,张晓平,等.醒脑益智胶囊对亚硝酸钠致小鼠记忆巩固障碍模型的影响.中药药理与临床,2013;(6)∶116~118
7 余资江,应大军,董世武.半乳糖急性致衰老动物模型剂量的探讨.解剖学杂志,2005; 28(4)∶422
8 杨斌.复方地黄对老年痴呆动物模型学习记忆能力的影响.中国实验方剂学杂志,2011; 17(3)∶195~197
9 李菲,郭蕾,乔之龙.补肾益智汤对老年痴呆模型大鼠治疗作用的实验研究.时珍国医国药,2010; 21(2)∶315~317
10 楚晋,李林.脑室灌注β-淀粉样肽致痴呆动物模型.中国药理学通报,2004; 20(7)∶827~829
11 钟树志,马世平,洪宗元.芍药苷活化Nrf2/ARE通路减轻Aβ(1-42)诱导的大鼠海马神经元损伤.药学学报,2013; 48(8)∶1353~1357
12 郑妮,汤宇,黎赛,等.新型复合式老年痴呆小鼠模型的建立.中南药学,2009; 7(7)∶481~484
13 李林,茹立强.丹参酮对D-半乳糖-Aβ_(1-40)致痴呆大鼠海马内Aβ和AChE的影响.中国老年学杂志,2010; 30(7)∶918~920
14 汪润,赵丽娟,王全英,等.β淀粉样蛋白1~42与D-半乳糖联合作用建立复合阿尔茨海默病样模型.解剖学报,2011; 42(4)∶461~464
15 张葳,张昱,赵晴,等.β-淀粉样蛋白对D-半乳糖致衰老大鼠学习记忆及海马超微结构的影响.吉林大学学报(医学版),2005;(2)∶246~248
16 Liu X J. Oxidative stress and Alzheimer's disease. Acta Physiologica Sinica,2012; 64(1)∶87~85
17 赵凡凡,周玉枝,高丽,等. D-半乳糖致衰老大鼠模型的研究进展.药学学报,2017,52(3)∶347~354
18 Abdel-Salam OM. Stem cell therapy for Alzheimer's disease. CNS Neurol Disord Drug Targets,2011; 10(4)∶459~485
19 秦大莲,岳永花,田吉,等.脑舒胶囊对阿尔茨海默病大鼠神经炎症损伤的保护.中国新药杂志,2010; 11∶986~990
20 王丹,张红英,兰艳.远志水提取物对小鼠学习记忆及血液学指标的影响.中国实验方剂学杂志,2012; 18(5)∶188~191
21 闫蓉,常翔,杨从,等.阿尔兹海默病β淀粉样蛋白形成和沉积的发病机制及中医药干预的可能途径.中药新药与临床药理,2012; 24(6)∶629~632
22 王爱梅,耿若君,李弋,等.旱莲草对老年痴呆模型大鼠学习记忆能力的影响及机制.中国老年学杂志,2016; 36(18)∶4413~4415
23 詹海涛,李海燕,曾煦欣,等.香港远志提取物对拟阿尔茨海默病大鼠学习记忆的影响及机制.中风与神经疾病杂志,2012; 29(3)∶243~245
24 Hachisu M,Konishi K,Hosoi M,et al. Beyond the Hypothesis of Serum Anticholinergic Activity in Alzheimer's Disease∶Acetylcholine Neuronal Activity Modulates Brain-Derived Neurotrophic Factor Production and Inflammation in the Brain. Neurodegener Dis,2015; 15(3)∶182~187
25 Choi D Y,Lee Y J,Hong J T,et al. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease. Brain Res Bull,2012; 87(2-3)∶144~53
2 郭力军,计德利,孙计桃,等.淫羊藿苷对AD模型大鼠神经元超微结构的影响.内蒙古医学杂志,2015; 47(6)∶657~660
3 周娇娇,阙建宇,于雯雯,等. Morris水迷宫检测动物学习记忆水平的方法学.中国老年学杂志,2017; 37(24)∶6274~6277
4 廖艺聪,李艳,王雷,等.小鼠避暗实验三种训练方法的效果比较.井冈山大学学报(自然科学版),2011; 32(04)∶101~103
5 Sasaki K,Han J,Shimozono H,et al. Caffeoylquinic acidrich purple sweet potato extract,with or without anthocyanin,imparts neuroprotection and contributes to the improvement of spatial learning and memory of SAMP8Mouse. J Agric Food Chem,2013; 61(21)∶5037~5045
6 侯林,李万忠,张晓平,等.醒脑益智胶囊对亚硝酸钠致小鼠记忆巩固障碍模型的影响.中药药理与临床,2013;(6)∶116~118
7 余资江,应大军,董世武.半乳糖急性致衰老动物模型剂量的探讨.解剖学杂志,2005; 28(4)∶422
8 杨斌.复方地黄对老年痴呆动物模型学习记忆能力的影响.中国实验方剂学杂志,2011; 17(3)∶195~197
9 李菲,郭蕾,乔之龙.补肾益智汤对老年痴呆模型大鼠治疗作用的实验研究.时珍国医国药,2010; 21(2)∶315~317
10 楚晋,李林.脑室灌注β-淀粉样肽致痴呆动物模型.中国药理学通报,2004; 20(7)∶827~829
11 钟树志,马世平,洪宗元.芍药苷活化Nrf2/ARE通路减轻Aβ(1-42)诱导的大鼠海马神经元损伤.药学学报,2013; 48(8)∶1353~1357
12 郑妮,汤宇,黎赛,等.新型复合式老年痴呆小鼠模型的建立.中南药学,2009; 7(7)∶481~484
13 李林,茹立强.丹参酮对D-半乳糖-Aβ_(1-40)致痴呆大鼠海马内Aβ和AChE的影响.中国老年学杂志,2010; 30(7)∶918~920
14 汪润,赵丽娟,王全英,等.β淀粉样蛋白1~42与D-半乳糖联合作用建立复合阿尔茨海默病样模型.解剖学报,2011; 42(4)∶461~464
15 张葳,张昱,赵晴,等.β-淀粉样蛋白对D-半乳糖致衰老大鼠学习记忆及海马超微结构的影响.吉林大学学报(医学版),2005;(2)∶246~248
16 Liu X J. Oxidative stress and Alzheimer's disease. Acta Physiologica Sinica,2012; 64(1)∶87~85
17 赵凡凡,周玉枝,高丽,等. D-半乳糖致衰老大鼠模型的研究进展.药学学报,2017,52(3)∶347~354
18 Abdel-Salam OM. Stem cell therapy for Alzheimer's disease. CNS Neurol Disord Drug Targets,2011; 10(4)∶459~485
19 秦大莲,岳永花,田吉,等.脑舒胶囊对阿尔茨海默病大鼠神经炎症损伤的保护.中国新药杂志,2010; 11∶986~990
20 王丹,张红英,兰艳.远志水提取物对小鼠学习记忆及血液学指标的影响.中国实验方剂学杂志,2012; 18(5)∶188~191
21 闫蓉,常翔,杨从,等.阿尔兹海默病β淀粉样蛋白形成和沉积的发病机制及中医药干预的可能途径.中药新药与临床药理,2012; 24(6)∶629~632
22 王爱梅,耿若君,李弋,等.旱莲草对老年痴呆模型大鼠学习记忆能力的影响及机制.中国老年学杂志,2016; 36(18)∶4413~4415
23 詹海涛,李海燕,曾煦欣,等.香港远志提取物对拟阿尔茨海默病大鼠学习记忆的影响及机制.中风与神经疾病杂志,2012; 29(3)∶243~245
24 Hachisu M,Konishi K,Hosoi M,et al. Beyond the Hypothesis of Serum Anticholinergic Activity in Alzheimer's Disease∶Acetylcholine Neuronal Activity Modulates Brain-Derived Neurotrophic Factor Production and Inflammation in the Brain. Neurodegener Dis,2015; 15(3)∶182~187
25 Choi D Y,Lee Y J,Hong J T,et al. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease. Brain Res Bull,2012; 87(2-3)∶144~53