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[金丝桃素对阿尔茨海默病模型小鼠学习记忆能力及海马区Aβ₁₋₄₂、βAPP和BACE1蛋白表达的影响]

[Effect of hyperforin on learning and memory abilities and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of Alzheimer's disease model mice].

作者信息

Geng Yan-Na, Wu Yi-Jun, Zhang Wen-Xin

机构信息

Department of Pharmacy, Huaihe Hospital of Henan University, Kaifeng 475000, China.

College of Pharmacy, Henan University, Kaifeng 475000, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2016 Aug;41(15):2877-2882. doi: 10.4268/cjcmm20161522.

Abstract

To investigate the effect of the hyperforin (HF) on learning and memory function and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of five-month-old APP/PS1 double transgenic mice, and discuss the underlying mechanism of HF. The five-month-old APP/PS1 double transgenic mice were randomly divided into the model group, rosiglitazone group (12 mg•kg⁻¹•d⁻¹) and HF high dose, middle dose and low dose groups (600, 300 and 150 mg•kg⁻¹•d⁻¹) in each group; in addition, 15C57BL/6J mice with the same months and background were selected as normal group. Drugs were diluted in the same volume before using, and then administrated by ig for 7 months, 1 time a day; the mice in normal group and model group received the same volume of distilled water. The learning and memory ability was tested by Morris water maze; Aβ₁₋₄₂, βAPP and BACE1proteinexpressionlevelswere tested by immunohistochemistry and Western blot. The Morris water maze results showed that as compared with the normal group, the learning and memory ability was significantly impaired in mice of model group (P<0.01); as compared with the model group, the learning and memory ability was improved in mice of rosiglitazone group and HF high, middle and low dose groups(P<0.01 or P<0.05). Immunohistochemistry and western blot results showed thatas compared with the normal group, the Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were significantly increased in mice of model group (P<0.01);as compared with the model group, Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were decreased in mice of rosiglitazone group and HF high, middle and low dose groups (P<0.01 or P<0.05). HF may improve the learning and memory ability of AD model mice via inhibition of βAPP and BACE1 protein expressions, thus reduced the generation of Aβ₁₋₄₂ proteins and amyloid plaque deposits in the brain.

摘要

探讨贯叶连翘素(HF)对5月龄APP/PS1双转基因小鼠学习记忆功能及海马区Aβ₁₋₄₂、β淀粉样前体蛋白(βAPP)和β-分泌酶1(BACE1)蛋白表达的影响,并探讨其潜在机制。将5月龄APP/PS1双转基因小鼠随机分为模型组、罗格列酮组(12 mg•kg⁻¹•d⁻¹)和HF高、中、低剂量组(600、300和150 mg•kg⁻¹•d⁻¹);另外,选取15只同月龄、相同背景的C57BL/6J小鼠作为正常组。给药前将药物用相同体积稀释,然后灌胃给药7个月,每天1次;正常组和模型组小鼠给予相同体积的蒸馏水。采用Morris水迷宫检测学习记忆能力;采用免疫组织化学和蛋白质印迹法检测Aβ₁₋₄₂、βAPP和BACE1蛋白表达水平。Morris水迷宫结果显示,与正常组相比,模型组小鼠学习记忆能力显著受损(P<0.01);与模型组相比,罗格列酮组和HF高、中、低剂量组小鼠学习记忆能力均有所改善(P<0.01或P<0.05)。免疫组织化学和蛋白质印迹结果显示,与正常组相比,模型组小鼠海马区Aβ₁₋₄₂、βAPP和BACE1蛋白表达水平显著升高(P<0.01);与模型组相比,罗格列酮组和HF高、中、低剂量组小鼠海马区Aβ₁₋₄₂、βAPP和BACE1蛋白表达水平均降低(P<0.01或P<0.05)。HF可能通过抑制βAPP和BACE1蛋白表达,减少脑内Aβ₁₋₄₂蛋白生成及淀粉样斑块沉积,从而改善AD模型小鼠的学习记忆能力。

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