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朝藿定降低阿尔茨海默病 APP 转基因小鼠模型中 APP 和 BACE-1 的表达,并减少 β-淀粉样蛋白负荷。

Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer's disease.

机构信息

Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.

出版信息

Int J Biol Sci. 2014 Jan 21;10(2):181-91. doi: 10.7150/ijbs.6232. eCollection 2014.

Abstract

OBJECTIVE

The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD).

METHODS

APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.

RESULTS

Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.

CONCLUSION

Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.

摘要

目的

本研究旨在探讨淫羊藿苷(一种传统中药淫羊藿的主要成分)对阿尔茨海默病(AD)淀粉样前体蛋白(APP)转基因(Tg)小鼠模型中β-淀粉样蛋白(Aβ)产生的影响及其药理学机制。

方法

APPV717I Tg 小鼠随机分为模型组和淫羊藿苷处理(30 和 100 μmol/kg/天)组。通过 Morris 水迷宫和物体识别试验测定学习记忆能力。通过酶联免疫吸附试验和免疫组织化学法测定 Aβ 含量。通过刚果红染色和 Bielschowsky 银染色检测淀粉样斑块。通过 Western blot 和免疫组织化学法测定 APP 和β-位点 APP 裂解酶 1(BACE-1)的表达水平。

结果

10 月龄 Tg 小鼠表现出明显的学习记忆障碍,海马区 Aβ 含量、淀粉样斑块和 APP、BACE-1 水平显著升高。淫羊藿苷灌胃 Tg 小鼠 6 个月(4 至 10 月龄)可改善学习记忆能力,显著降低海马区 Aβ 含量、淀粉样斑块和 APP、BACE-1 水平。

结论

淫羊藿苷通过降低 APP 和 BACE-1 水平,减少 APP 转基因小鼠海马区的 Aβ 负荷和淀粉样斑块沉积。这些新发现表明,淫羊藿苷可能是 AD 患者有希望的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c97/3927130/b52c057fe3cd/ijbsv10p0181g001.jpg

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