复方丹参片早期干预对APP/PS1转基因小鼠的学习记忆影响

神经药理学报 ›› 2014, Vol. 4 ›› Issue (5): 1-7.

• 研究论文 • 下一篇

复方丹参片早期干预对APP/PS1转基因小鼠的学习记忆影响

刘旻, 郭海彪, 李楚源, 王德勤, 徐江平, 覃仁安

1. 广州白云山和记黄埔中药有限公司，广州，510515，中国
2. 南方医科大学药学院神经药理学科，广州，510515，中国

出版日期:2014-10-26 发布日期:2015-01-20
通讯作者: 徐江平，男，博士生导师；研究方向：神经药理学；电话/传真：020-61648235; E-mail: jpx@smu.edu.cn 覃仁安，男，研究方向：神经药理学：E-mail: qinrenan@813zy.com
作者简介:刘旻，男，博士；研究方向：神经药理学；E-mail: liumin@813zy.com
基金资助:
十二五重大新药创制中药大品种复方丹参片系统研究及技术改造(No.2011ZX09201)

Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice

Liu Min, Guo Hai-biao, Li Chu-yuan, Wang De-qin, Xu Jiang-ping, Qin Ren-an

1. Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd, Guangzhou, 510515, China
2. Department of Neuropharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

Online:2014-10-26 Published:2015-01-20
Contact: 徐江平，男，博士生导师；研究方向：神经药理学；电话/传真：020-61648235; E-mail: jpx@smu.edu.cn 覃仁安，男，研究方向：神经药理学：E-mail: qinrenan@813zy.com
About author:刘旻，男，博士；研究方向：神经药理学；E-mail: liumin@813zy.com
Supported by:
十二五重大新药创制中药大品种复方丹参片系统研究及技术改造(No.2011ZX09201)

摘要/Abstract

摘要： 目的: 探讨复方丹参片对APP/PS1转基因小鼠学习记忆的影响及作用机制。方法: 4月龄野生型小鼠和APP/PS1转基因小鼠分别灌胃给予溶剂或药物8周后,采用新物体识别试验和跳台试验评价复方丹参片对小鼠行为学表现的影响；应用ELISA检测小鼠海马淀粉样蛋白Aβ40、Aβ42的含量；Real time PCR和Western blot分别检测IDE/NEP的mRNA和蛋白水平变化。结果：新物体识别试验结果显示，复方丹参片720 mg·kg-1显著性增加APP/PS1转基因小鼠对新物体的识别指数。跳台实验结果显示，复方丹参片720，360 mg·kg-1显著性减少APP/PS1转基因小鼠学习次数，此外，复方丹参片720 mg·kg-1明显增加小鼠在平台的停留时间。ELISA结果显示，复方丹参片720，360 mg·kg-1显著性降低APP/PS1转基因小鼠海马Aβ40、Aβ42水平。Real time PCR结果显示，复方丹参片720 mg·kg-1显著性上调APP/PS1转基因小鼠海马胰岛素分解酶(insulin degrading enzyme, IDE)和脑啡肽酶(neprilysin, NEP) mRNA的表达。Western blot结果显示，复方丹参片720 mg·kg-1显著性增加小鼠海马IDE蛋白表达。结论：复方丹参片改善APP/PS1转基因小鼠学习记忆能力，可能与减少海马Aβ水平和增加IDE的表达有关。

关键词: 老年痴呆症, APP/PS1转基因小鼠, 复方丹参片, &, beta, -淀粉样蛋白, 胰岛素分解酶, 脑啡肽酶

Abstract: Objective: To investigate effect of compound danshan tablet (CDST) on learning and memory in APP/PS1 transgenic mice and the underlying mechanism. Methods: APP/PS1 transgenic mice at the age of 4 months were orally administered with vehicle or CDST or donepezil for 8 weeks, then the behavioral performance of mice was tested using novel object recognition and step-down passive avoidance. Aβ40 and Aβ42 level in the hippocampus of wild-type mice and APP/PS1 mice were determined by ELISA assay. Real time PCR and Western blot were used to examine mRNA and protein expression of insulin degrading enzyme (IDE) and neprilysin (NEP) respectively. Results: Result of novel object recognition test showed that CDST (720 mg·kg-1) significantly increased the recognition index for the novel object in APP/PS1 mice. Step-down passive avoidance suggested that CDST (720，360mg·kg-1)-treated APP/PS1 mice significantly decreased the latency to stay on the platform. In addition, APP/PS1 mice treated by CDST (720 mg·kg-1) significantly increased retention on the platform. ELISA analysis showed that CDST (720，360mg·kg-1) decreased the level of Aβ40 and Aβ42 in the hippocampus of APP/PS1 mice. In Real time PCR, CDST (720mg·kg-1) statistically increased the mRNA expression of IDE and NEP in the hippocampus of APP/PS1 mice. Western blot analysis indicated that CDST (720mg·kg-1) significantly increased IDE expression in APP/PS1 mice. Conclusion: Improvement of learning and memory by CDST in APP/PS1 mice may be associated with the decreased of Aβ and increased of IDE expression.

Key words: Alzheimer&, rsquo, s disease (AD), APP/PS1 transgenic mice, Compound danshen tablet (CDST), &, beta, -amyloid (A&, beta, ), Insulin degrading enzyme (IDE), Neprilysin (NEP)

中图分类号:

R965

刘旻, 郭海彪, 李楚源, 王德勤, 徐江平, 覃仁安. 复方丹参片早期干预对APP/PS1转基因小鼠的学习记忆影响[J]. 神经药理学报, 2014, 4(5): 1-7.

Liu Min, Guo Hai-biao, Li Chu-yuan, Wang De-qin, Xu Jiang-ping, Qin Ren-an. Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice[J]. Acta Neuropharmacologica, 2014, 4(5): 1-7.

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复方丹参片早期干预对APP/PS1转基因小鼠的学习记忆影响

Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice

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