2023 年第 7 期 第 18 卷

参芪醒脑浸膏对阿尔茨海默病模型小鼠认知功能障碍的改善作用及机制研究

Improvement effect and mechanism of Shenqi Xingnao extractum on cognitive dysfunction in Alzheimer′s disease model mice

作者：李雅莉杨翠翠张兰

英文作者：Li Yali Yang Cuicui Zhang Lan

单位：首都医科大学宣武医院药学部北京市老年病医疗研究中心北京市神经药物工程研究中心，北京100053

英文单位：Department of Pharmacy Xuanwu Hospital Capital Medical University Beijing Geriatric Medical Research Center Beijing Engineering Research Center for Nerve System Drugs Beijing 100053 China

关键词：参芪醒脑浸膏；D-半乳糖；阿尔茨海默病；认知功能障碍；神经元损伤

英文关键词：ShenqiXingnaoextractum;D-galactose;Alzheimer′sdisease;Cognitivedysfunction; Neuronalinjury

• 摘要：

• 目的  探讨参芪醒脑浸膏对D-半乳糖诱导脑老化致阿尔茨海默病（AD）模型小鼠认知功能障碍的改善作用及机制。方法  选取无特定病原体级美国癌症研究所小鼠110只，随机分为对照组（16只）、大剂量对照组（15只）、模型组（17只）、小剂量组（16只）、中剂量组（16只）、大剂量组（16只）及多奈哌齐组（14只）。除对照组、大剂量对照组外，其余小鼠使用D-半乳糖溶液颈背部皮下注射，连续注射65 d制备AD小鼠模型。于造模当日开始灌胃给药，小剂量组予参芪醒脑浸膏3.5 g生药/kg，中剂量组予参芪醒脑浸膏7 g生药/kg，大剂量对照组、大剂量组予参芪醒脑浸膏14 g生药/kg，多奈哌齐组予多奈哌齐1 mg/kg，对照组、模型组予相同容积的蒸馏水，均为1次/d，连续给药65 d。采用Morris水迷宫实验及物体识别实验评价小鼠的空间学习记忆及识别记忆能力。采用蛋白质印迹法检测小鼠大脑皮质和海马组织内神经元核抗原（NeuN）、神经生长因子（NGF）的表达水平。结果模型组第3~5天逃避潜伏期长于对照组（均P＜0.05），小、中、大剂量组第3~5天及多奈哌齐组第3~4天逃避潜伏期均短于模型组（均P＜0.05）。模型组辨别指数低于对照组［（-0.010±0.191）比（0.170±0.180）］（P＜0.05），中、大剂量组及多奈哌齐组辨别指数［（0.240±0.206）、（0.278±0.089）、（0.192±0.210）］均高于模型组（均P＜0.01）。模型组大脑皮质和海马组织NeuN、NGF表达水平均低于对照组（均P<0.05），小、中、大剂量组及多奈哌齐组大脑皮质NeuN、NGF表达水平及小、中、大剂量组海马组织NGF表达水平均高于模型组（均P<0.05）。结论  参芪醒脑浸膏可以通过保护神经元进而在D-半乳糖诱导的脑老化致AD小鼠模型中发挥良好的抗认知功能障碍的效果。

• Objective  To investigate the improvement effect and mechanism of Shenqi Xingnao extractum on cognitive dysfunction in Alzheimer′s disease (AD) mice caused by D-galactose-induced brain aging. Methods  Totally 110 mice without specific pathogens were selected from the American cancer institute. They were randomly divided into control group (16 mice), high-dose control group (15 mice), model group (17 mice), low-dose group (16 mice), middle-dose group (16 mice), high-dose group (16 mice) and donepezil group (14 mice). Except for control group and high-dose control group, the remaining mice were injected subcutaneously with D-galactose solution on the back of their necks for 65 d consecutively to prepare the AD mouse model. Gastric gavage was started on the day of modeling, low-dose group was given Shenqi Xingnao extractum 3.5 g raw herb/kg, middle-dose group was given Shenqi Xingnao extractum 7 g raw herb/kg, high-dose control group and high-dose group were given Shenqi Xingnao extractum 14 g raw herb/kg, donepezil group was given donepezil 1 mg/kg, and control group and model group were given same volume of distilled water. All were administered once a day for 65 d. Morris water maze test and object recognition test were used to evaluate the spatial learning memory and recognition memory ability of mice. Western blotting was used to detect the expression levels of neuronal nuclear antigen (NeuN) and nerve growth factor (NGF) in cerebral cortex and hippocampus tissue of mice. Results  The escape incubation period in model group was longer than that in control group from the 3rd to 5th d (all P<0.05), and the escape incubation periods in low-, middle- and high-dose groups from the 3rd to 5th d and donepezil group from the 3rd to 4th d were shorter than those in model group (all P<0.05). The discrimination index in model group was lower than that in control group ［（-0.010±0.191） vs （0.170±0.180）］(P<0.05), and the discrimination index in middle- and high-dose groups and donepezil group ［（0.240±0.206）,（0.278±0.089）,（0.192±0.210）］ were higher than that in model group (all P<0.01). Expression levels of NeuN and NGF in cerebral cortex and hippocampus tissue in model group were lower than those in control group (all P<0.05). Expression levels of NeuN and NGF in cerebral cortex in low-, middle- and high-dose groups and donepezil group and the expression of NGF in hippocampus tissue in low-, middle- and high-dose groups were higher than those in model group (all P<0.05). Conclusions    henqi Xingnao extractum can play a good effect on anti-cognitive dysfunction in AD mice model caused by D-galactose-induced brain aging by protecting neurons.