中国中药杂志

2016, v.41(07) 1269-1274

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6首开心散类方对阿尔兹海默病模型小鼠的药理作用及机制研究
Effect of six class of Kaixin San formulas on pharmacological and preliminary mechanism of Alzheimer's disease mice

李牧函;张静;赵润清;董宪喆;胡园;陈婷;李洁;刘俐;刘屏;
LI Mu-han;ZHANG Jing;ZHAO Run-qing;DONG Xian-zhe;HU Yuan;CHEN Ting;LI Jie;LIU Li;LIU Ping;Beijing University of Chinese Medicine;Department of Clinical Pharmacology and Pharmacy,Chinese PLA General Hospital;

摘要(Abstract):

该文研究组方相同配比不同的6个开心散类方对阿尔茨海默病(AD)模型小鼠学习记忆能力的改善作用,以及对阿尔茨海默病模型小鼠海马中的海马中脑源性神经营养因子(BDNF),Tau蛋白,p-Tau蛋白,Aβ,乙酰胆碱(Ach),乙酰胆碱酯酶(Ach E)及血清中N端前脑钠肽前体(NT-pro BNP)的影响,选用昆明小鼠,腹腔注射D-半乳糖和亚硝酸钠,建立阿尔茨海默小鼠模型后,连续灌胃35 d,其中阳性药为石杉碱甲(0.05 mg·kg-1),各开心散类方给药组高、中、低剂量分别为3.570,1.785,0.892 g·kg-1,采用Morris水迷宫评价各组动物学习记忆能力;Western blot方法检测各组小鼠海马中BDNF的含量;Elisa方法检测各组小鼠海马中Tau蛋白,p-Tau蛋白,Aβ,Ach,Ach E及血清中NT-pro BNP的含量。结果显示,《千金要方·卷十四》之开心散显著改善AD模型小鼠学习记忆能力,明显升高其海马中BDNF,Ach含量,显著降低其海马中Ach E,Aβ,Tau蛋白,p-Tau蛋白,NT-pro BNP含量,作用最为全面,在Tau蛋白方面作用较突出;《医心方》之开心散、《医门方》之开心丸、《备急千金要方》之定志小丸和《古今录验》之定志丸对AD模型小鼠各指标的影响各有侧重,部分剂量显著优化了评价学习记忆能力的各项指标,明显升高AD模型小鼠海马中BDNF,Ach含量,显著降低AD模型小鼠海马中Aβ,Tau蛋白,p-Tau蛋白含量及Ach E活性,明显降低AD模型小鼠血清中NT-pro BNP含量,作用较为显著;《千金翼》之补心汤的高、中、低剂量均基本未见其对阿尔茨海默病模型动物的影响。结果表明,《千金要方·卷十四》之开心散对阿尔茨海默病模型小鼠的作用最为全面,且在Tau蛋白方面的作用较为突出。
The efficacy of Chinese herbal formulas in treating Alzheimer has been proved in many studies. In this study,six different Kaixin San formulas were compared to investigate their effects on learning and memory decline,brain-derived neurotrophic factor( BDNF) in the hippocampus,tau protein,acetylcholinesterase( ACh E) and N-terminal pro-brain natriuretic peptide( NT-pro BNP).Kunming mice were selected and established a mouse model of Alzheimer' s by intraperitoneal injection of D-galactose and sodium nitrite,continued intragastric 4 weeks,using the ability of learning and memory in Morris water maze test to evaluate the animals in each group; the content of BDNF in the hippocampus of mice with Western blotting detected; ELISA method for the detection of each group of mice hippocampal tau protein,p-Tau protein,Aβ,Ach,Ach E and serum NT-pro BNP levels. The results showed that,Kaixin San of Qianjin Yaofang three dose recorded significantly improved learning and memory ability of mice; increased the content of BDNF and Ach in the hippocampus; decreased the content of Aβ,Tau protein,p-Tau protein in the hippocampus; high,middle dose significantly decreased the serum NT-pro BNP and Ach E in hippocampus,the effect is most significant. Part dose of Kaixin San of Yixin Fang,Kaixin Wan of Yimen Fang,Dingzhi Xiaowan of Beji Qianjin Yaofang and Dingzhi Wan of Guji Luyan could improve the learning and memory ability evaluation indicators,significantly increased BDNF and Ach in the hippocampus of AD model mice,reduced the Aβ,Tau protein,p-Tau protein in hippocampus of AD model mice,decreased the NT-pro BNP and Ach E in serum of AD mice,the effect is more significant. Three does of Buxin Tang of Qianjin Yi had no effects of treatment in Alzheimer' s disease. The results showed the treatment in AD of Kaixin San of Qianjin Yaofang is the most significant.

关键词(KeyWords): 开心散类方;阿尔茨海默病;阿尔茨海默病小鼠模型;Tau蛋白
Kaixin San formulas;Alzheimer;Alzheimer disease mouse model;Tau protein

Abstract:

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基金项目(Foundation): 国家自然科学基金项目(81373996)

作者(Author): 李牧函;张静;赵润清;董宪喆;胡园;陈婷;李洁;刘俐;刘屏;
LI Mu-han;ZHANG Jing;ZHAO Run-qing;DONG Xian-zhe;HU Yuan;CHEN Ting;LI Jie;LIU Li;LIU Ping;Beijing University of Chinese Medicine;Department of Clinical Pharmacology and Pharmacy,Chinese PLA General Hospital;

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