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

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

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。

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.