贯叶金丝桃素对AD模型小鼠学习记忆能力及海马组织中Aβ_(1-42),βAPP及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

该文研究贯叶金丝桃素(HF)对5月龄APP/PS1双转基因小鼠学习记忆能力及海马组织中β-淀粉样蛋白1-42(Aβ1-42)、β淀粉样前体蛋白(βAPP)及β位点剪切酶1(BACE1)蛋白表达的影响,并初步探讨其作用机制。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)及HF高、中、低剂量组(600,300,150 mg·kg^(-1)·d^(-1)),每组15只;另选15只同周龄同背景C57BL/6J小鼠设为正常对照组。药物使用前均稀释相同体积,采用灌胃给药,正常组及模型组给予同体积蒸馏水,每日1次,连续给药7个月。Morris水迷宫法检测AD模型小鼠学习记忆能力的变化,免疫组织化学方法和Western blot技术测定Aβ1-42,βAPP及BACE1的蛋白表达水平。Morris水迷宫结果提示,与正常组相比,模型组小鼠的学习记忆能力显著下降(P<0.01);与模型组相比,HF各组及罗格列酮组小鼠学习记忆能力均有提高(P<0.01或P<0.05);免疫组织化学和Western blot技术检测结果表明,与正常组相比,模型组小鼠海马CA1区Aβ_(1-42),βAPP及BACE1蛋白表达均明显增加(P<0.01);与模型组相比,HF各组及罗格列酮组小鼠海马CA1区Aβ_(1-42),βAPP及BACE1蛋白表达均有减少(P<0.01或P<0.05)。HF改善AD模型小鼠学习记忆能力的机制可能是通过抑制脑内βAPP及BACE1蛋白的表达,从而减少AD模型小鼠脑内Aβ_(1-42)蛋白的生成及淀粉样斑块沉积。

To investigate the effect of the hyperforin （HF） on learning and memory function and Aβ1-42, flAPP 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 BACElproteinexpressionlevelswere 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 13APP and BACE1 protein expressions, thus reduced the generation of Aβ1-42 proteins and amyloid plaque deposits in the brain.