灯盏乙素对阿尔茨海默病小鼠脑组织β分泌酶途径相关蛋白表达的影响  

Effect of scutellarin on expression of Aβ generation pathway-related protein in brain tissues of model mice with Alzheimer's disease

作　　者：王豫君 敖俊文 郭莉莉 于燕妮[1] WANG Yujun;AO Junwen;GUO Lili;YU Yanni(Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学,贵阳550004 [2]贵阳市第一人民医院

出　　处：《山东医药》2018年第26期5-8,共4页Shandong Medical Journal

基　　金：国家自然科学基金项目(30870986)

摘　　要：目的观察灯盏乙素(Scu)对阿尔茨海默病(AD)小鼠脑组织中β淀粉样肽(Aβ)生成途径中β分泌酶途径相关蛋白的影响。方法取类AD动物模型APPswe/PS1d E9双转基因小鼠40只,分为Scu低、中、高剂量组和模型组各10只,另取C57BL/6J小鼠10只作为正常对照组。Scu低、中、高剂量组分别给予Scu 1.5、2.5、4.0 mg/(100 g·d)灌胃,正常对照组和模型组给予等量生理盐水灌胃,连续90 d。治疗后采用Morris水迷宫检测学习记忆能力,第1~4天进行定向航行试验,记录逃避潜伏期,第5天进行空间探索实验,记录第1次穿越原站台时间及1min内穿过原站台位置的次数。小鼠断颈处死,采集脑组织标本,Western blotting法检测β淀粉样前体蛋白(APP)、β淀粉样前体蛋白裂解酶1(BACE1)、BACE2蛋白表达,Real-time PCR法检测APP、BACE1、BACE2 mRNA表达。结果与正常对照组相比,模型组在定向航行中逃避潜伏期时间延长,第1次穿越平台时间明显延长,平台穿越次数减少(P均<0.01);与模型组比较,高剂量Scu组逃避潜伏期时间缩短,第1次穿越平台时间缩短,平台穿越次数增多(P均<0.01)。中、低剂量组与模型组比较无统计学差异(P均>0.05)。与正常对照组相比,模型组脑组织中APP和BACE1蛋白及mRNA表达升高,BACE2蛋白表达水平下降;Scu高剂量组脑组织中APP和BACE1蛋白及mRNA表达降低,BACE2蛋白表达水平升高(P均<0.05)。各组脑组织中BACE2 mRNA表达无统计学差异(P均>0.05)。结论 Scu能够调节AD小鼠Aβ生成途径中主要因子APP、BACE1蛋白和mRNA以及BACE2蛋白表达,通过干预APP代谢的β分泌酶途径来抑制Aβ生成。Objective To observe the effect of scutellarin（ Scu） on the expression of β-amyloid protein（ Aβ） generation pathway-related proteins in the brain tissues of model mice with Alzheimer＇s disease（ AD）. Methods Forty AD model mice（ APPswe/PS1 d E9 double transgenic mice） were divided into the following groups： the control group（ C57 BL/6 J mice）,model group（ APPswe/PS1 d E9 mice）,and low-dose,medium-dose,and high-dose Scu groups（ APPswe/PS1 d E9 mice）.The mice in the Scu groups were administered 1. 5,2. 5,and 4. 0 mg/（ 100 g·d） while the other two groups were given the equal dose of normal saline for 90 days. The learning and memory ability of the mice were detected by Morris water maze. On day 1-4,the place navigation tests were detected,and then we did the spatial probe tests on day 5,we recorded the time of first crossing the original station,and the number of times passing through the original station within 1 min. The protein and mRNA expression of β-amyloid precursor protein（ APP）,β-site APP-cleaving enzyme1 and 2（ BACE1/2） in the brain tissues were detected by Western blotting and real-time PCR. Results Compared with the control group,the mean escape latency and the time of first crossing the original station of model group were extended,and the times of crossing platform were decreased（ all P〈0. 01）; compared with the model group,the mean escape latency and the time of first crossing the original station of the high-dose Scu group were shortened,and the times of crossing platform were increased（ all P〈0. 01）. No significant difference was found between the model group and the medium-dose,low-dose Scu groups（ all P〈0. 05）. Compared with the control group,the expression of APP and BACE1 protein and mRNA in the brain tissues of the model group were increased,and the protein expression level of BACE2 was decreased. After treatment with high-dose Scu,the result was exactly the opposite. There were no significant differences in BACE2 mRNA expression

关 键 词：阿尔茨海默病 灯盏乙素 Β淀粉样肽 淀粉样前体蛋白 β淀粉样前体蛋白裂解酶 双转基因小鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]