复方丹参片早期干预对APP/PS1转基因小鼠学习记忆的影响  

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

作　　者：刘旻[1,2,3] 郭海彪[2] 李楚源[1] 王德勤[1] 徐江平[2] 覃仁安[1] 

机构地区：[1]广州白云山和记黄埔中药有限公司 [2]南方医科大学药学院 [3]广药集团博士后科研工作站

出　　处：《神经药理学报》2014年第5期1-7,共7页Acta Neuropharmacologica

基　　金：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项目(No.2011ZX09201)

摘　　要：目的:探讨复方丹参片早期干预对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,采用新物体识别实验和跳台实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β淀粉样蛋白(β-amyloid protein,Aβ)Aβ40、Aβ42的含量;采用Real time PCR和Western blot分别检测胰岛素分解酶(insulin degrading enzyme,IDE)/脑啡肽酶(neprilysin,NEP)m RNA和蛋白水平的变化。结果:新物体识别实验结果显示,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IDE和NEP m RNA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:复方丹参片可改善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。Objective：To investigate effect of compound danshen 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-l） significantly increased the recognition index for the novel object in APP/ PS1 mice. Step-down passive avoidance suggested that CDST （720, 360 mg·kg-1）-treated APP/ PS 1 mice significantly decreased the latency to stay on the platform. In addition,APP/PS 1 mice treated by CDST （720 mg·kg-1） significantly increased retention on the platform. ELISA analysis showed that CDST （720, 360 mg·kg-1） decreased the level of Aβ40 and Aβ42 in the hippocampus of APP/PS1 mice. In Real time PCR,CDST （720 mg.kg-1） statistically increased the mRNA expression of IDE and NEP in the hippocampus ofAPP/PS 1 mice. Western blot analysis indicated that CDST （720 mg·kg-1） significantly increased IDE expression in APP/PS1 mice. Conclusion： Improvement of learning and memory by CDST in APP/PSI mice may be associated with the decreased of Aβ and increased of IDE expression.

关 键 词：阿尔茨海默病 APP/PS1转基因小鼠 复方丹参片 Β-淀粉样蛋白 胰岛素分解酶 脑啡肽酶 

分 类 号：R965[医药卫生—药理学]