中成药2024,Vol.46Issue(1) :72-78.DOI:10.3969/j.issn.1001-1528.2024.01.013

十全大补汤通过调节突触功能对阿尔兹海默病小鼠认知损伤的改善作用

Effects of Shiquan Dabu Decoction on cognitive impairment in a mouse model of Alzheimer's disease through regulation of synaptic function

郭自贺 王祎 朱梦姚 袁海阳 吕馨 贡岳松
中成药2024,Vol.46Issue(1) :72-78.DOI:10.3969/j.issn.1001-1528.2024.01.013

十全大补汤通过调节突触功能对阿尔兹海默病小鼠认知损伤的改善作用

Effects of Shiquan Dabu Decoction on cognitive impairment in a mouse model of Alzheimer's disease through regulation of synaptic function

郭自贺 1王祎 1朱梦姚 1袁海阳 1吕馨 1贡岳松2
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作者信息

  • 1. 南京中医药大学, 江苏 南京 210046
  • 2. 南京中医药大学, 江苏 南京 210046;江苏鹏鹞药业新药创新中心, 江苏 宜兴 214200
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摘要

目的 探究十全大补汤对阿尔兹海默病(AD)小鼠突触功能及认知损伤的改善作用.方法 60 只小鼠随机分为对照组、模型组、美金刚组(5 mg/kg)和十全大补汤高、中、低剂量组(6.24、3.12、1.56 g/kg),每组 10 只,除对照组外,其余各组小鼠腹腔注射D-半乳糖并灌胃AlCl3 70 d建立AD模型,造模第29 天开始,各组灌胃给予相应剂量药物 42 d.通过Morris水迷宫实验和条件恐惧实验检测空间学习记忆及联想记忆,HE染色观察海马神经元形态改变情况,试剂盒检测血清SOD活性、MDA水平及海马组织SOD、AChE活性,MDA、ACh、TNF-α、IL-1β水平,Western blot法检测海马组织PSD-95、Shank3、NR1、NR2A、NR2B、AMPK、p-AMPK蛋白表达.结果 与模型组比较,十全大补汤高剂量组小鼠空间学习记忆能力与联想记忆提升(P<0.05,P<0.01),海马神经元病理损伤减轻,氧化应激及炎症水平下降(P<0.05,P<0.01),胆碱能传递增强(P<0.05,P<0.01),海马组织 PSD-95、Shank3、NR1、NR2A、NR2B、p-AMPK蛋白表达升高(P<0.05,P<0.01).结论 十全大补汤可改善AD小鼠认知损伤,其机制可能与激活AMPK,恢复突触功能有关.

Abstract

AIM To explore the effects of Shiquan Dabu Decoction on the synaptic function and cognitive impairment in a mouse model of Alzheimer's disease(AD).METHODS Sixty mice were randomly divided into the control group,the model group,the memantine group(5 mg/kg)and the high,medium and low dose Shiquan Dabu Decoction groups(6.24,3.12 and 1.56 g/kg),with 10 mice in each group.Except for those of the control group,the mice of other groups underwent their 70-day AD models induction by intraperitoneal injection of D-galactose and gavage feeding of AlCl3,followed by 42-day corresponding dosing of drugs by gavage on the 29th day.The mice had their spatial learning and associative memory detected by Morris water maze test and conditioned fear test;their morphological changes of hippocampal neurons observed by HE staining;their serum SOD activity,MDA level,and SOD,AChE activities and MDA,ACh,TNF-α and IL-1β levels in hippocampus detected by kits;and their PSD-95,Shank3,NR1,NR2A,NR2B,AMPK and p-AMPK protein expressions in hippocampus detected by Western blot.RESULTS Compared with the model group,the high-dose Shiquan Dabu Decoction group displayed improved spatial learning and memory ability and associative memory(P<0.05,P<0.01);reduced pathological damage of hippocampal neurons,decreased levels of oxidative stress and inflammation(P<0.05,P<0.01);enhanced cholinergic transmission(P<0.05,P<0.01),and increased protein expressions of PSD-95,Shank3,NR1,NR2A,NR2B,and p-AMPK in hippocampal tissue(P<0.05,P<0.01).CONCLUSION Shiquan Dabu Decoction can improve the cognitive impairment of in the mouse model of AD,and its mechanism may be related to AMPK activation and synaptic function restoration.

关键词

十全大补汤/阿尔兹海默病/学习记忆能力/氧化应激/神经炎症/突触功能/AMPK

Key words

Shiquan Dabu Decoction/Alzheimer's disease/learning and memory ability/oxidative stress/neuroinflammation/synaptic function/AMPK

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基金项目

江苏省双创计划项目(013033004004A)

南京中医药大学高级人才科研启动项目(013074004016)

出版年

2024
中成药
国家食品药品监督管理局,信息中心中成药信息站,上海中药行业协会

中成药

CSTPCDCSCD北大核心
影响因子:1.217
ISSN:1001-1528
参考文献量3
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