药学学报, 2019, 54(4): 660-669
引用本文:
张静, 史旭芹, 周桂生, 谭亚杰, 陈嘉倩, 陶慧娟, 濮宗进, 刘培, 朱悦, 钱大玮, 唐于平, 段金廒. 基于主成分分析和多指标综合指数法对银杏酮酯-多奈哌齐不同量比抗痴呆作用比较研究[J]. 药学学报, 2019, 54(4): 660-669.
ZHANG Jing, SHI Xu-qin, ZHOU Gui-sheng, TAN Ya-jie, CHEN Jia-qian, TAO Hui-juan, PU Zong-jin, LIU Pei, ZHU Yue, QIAN Da-wei, TANG Yu-ping, DUAN Jin-ao. Comparative study on the effects of different proportions of ginkgo ketoester and donepezil on anti-dementia based on principal component analysis and multi-attribute comprehensive index methods[J]. Acta Pharmaceutica Sinica, 2019, 54(4): 660-669.

基于主成分分析和多指标综合指数法对银杏酮酯-多奈哌齐不同量比抗痴呆作用比较研究
张静1, 史旭芹1, 周桂生1, 谭亚杰1, 陈嘉倩1, 陶慧娟1, 濮宗进1, 刘培1, 朱悦1, 钱大玮1, 唐于平1,2, 段金廒1
1. 南京中医药大学, 江苏省中药资源产业化过程协同创新中心, 江苏省方剂高技术研究重点实验室, 中药资源产业化与方剂创新药物国家地方联合工程研究中心, 江苏 南京 210023;
2. 陕西中医药大学, 陕西省中医药管理局中药配伍重点研究室, 陕西 西安 712046
摘要:
比较评价银杏酮酯-多奈哌齐(GD)不同量比对痴呆小鼠学习和记忆能力的影响,优选银杏酮酯-多奈哌齐治疗痴呆作用的最佳配比。实验方案经南京中医药大学动物实验伦理委员会批准,所有程序均严格按照动物使用和护理的伦理原则进行。本研究采用多因素神经损伤复制痴呆小鼠模型,通过Morris水迷宫行为学、脑组织病理学切片以及血浆和脑组织中的神经递质及相关酶指标的变化,观察两药不同量比对痴呆小鼠学习记忆能力的影响。采用主成分分析法和多指标综合指数法综合评价银杏酮酯-多奈哌齐不同量比抗痴呆的总效应。结果表明,基于临床常用配比(1:1)7个剂量下,两药联用1倍量(临床等效量)时效果最好;基于最佳剂量下两药联用11个配比中,以银杏酮酯-多奈哌齐1:1的总改善效果最好,这与临床1:1使用两药结论相一致,为临床更有效应用银杏酮酯和多奈哌齐提供科学依据。
关键词:    黄酮      银杏内酯      多奈哌齐      配比      痴呆      主成分分析      多指标综合指数法     
Comparative study on the effects of different proportions of ginkgo ketoester and donepezil on anti-dementia based on principal component analysis and multi-attribute comprehensive index methods
ZHANG Jing1, SHI Xu-qin1, ZHOU Gui-sheng1, TAN Ya-jie1, CHEN Jia-qian1, TAO Hui-juan1, PU Zong-jin1, LIU Pei1, ZHU Yue1, QIAN Da-wei1, TANG Yu-ping1,2, DUAN Jin-ao1
1. Jiangsu Provincial Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China;
2. Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, China
Abstract:
The combination of ginkgo ketoester tablet-donepezil (GD) is a popular combination commonly used in clinic for the treatment of Alzheimer's disease. To evaluate the learning and memory improving ability of different proportions of the two drugs. We optimized the ratio of GD for treatment of dementia using a mouse model. Dementia was induced by multiple neuronal damages in mice. The experimental protocols were approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine and all the procedures were strictly conducted in accordance with ethical principle of animal use and care. Morris water maze, brain hematosylin-eosin staining and the changes of the neurotransmitters and related enzymes in the plasma or brain tissues were tested to determine the effect of GD on dementia mice. The results showed that the dementia mice were significantly different from the normal group in terms of behavior, pathological sections and related indicators. Compared to the dementia mice, partial administration groups could improve learning and memory ability as well as indexes in the blood and brain tissues. Both the principal component analysis and multi-attribute comprehensive index methods were used to comprehensively evaluate the total effect of GD on anti-dementia. The results showed that the combination of two drugs at the dose of 0.5 to 1 times was in a dose-effect relationship, and the dose of 1 (the clinical equivalent) had the best treatment effect. Then based on the optimal dose, GD 1:1 had best effect, which was consistent with the clinical use of two drugs. This provides scientific basis for more effective application of the compatibility between ketoester tablet and donepezil for modern clinic medicine.
Key words:    flavonoid    ginkgolide    donepezil    compatibility    dementia    principal component analysis    multi-attribute comprehensive index method   
收稿日期: 2018-09-28
DOI: 10.16438/j.0513-4870.2018-0885
基金项目: 国家自然科学基金资助项目(81803699);江苏省自然科学基金资助项目(BK20171068);江苏省中药资源产业化过程协同创新中心开放课题(012092002006-4);江苏省333高层次人才资助项目(BRA2016387);江苏省高校优势学科建设工程资助项目(PAPD).
通讯作者: 周桂生, 唐于平
Email: zhouguisheng1@126.com;2051001@sntcm.edu.cn
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