中文摘要：

目的 探讨Aβ3-10重复片段质粒免疫接种3月龄APPswe/PSEN1双转基因（AD）鼠脑内BACE1的影响。方法 应用Aβ3-10重复片段质粒免疫3月龄APPswe/PSEN1双转基因鼠,同等剂量的PBS免疫对照组及C57BL/6J组小鼠,各组小鼠均在免疫后2、4、6次后通过RT-PCR法检测BACE1 m RNA水平,Western blotting法检测BACE1/GFAP/NF-κB蛋白水平,免疫组化法观察Aβ1-42脑内分布情况。水迷宫检测其行为学改变。结果在免疫2次后BACE1 m RNA表达水平C57BL/6J组〈Aβ3-10组〈对照组（F=4.649,P=0.021）;免疫4次Aβ3-10组〈C57BL/6J组〈对照组（F=115.683,P=0.001）;免疫6次C57BL/6J组〈Aβ3-10组〈对照组（F=86.600,P〈0.001）。BACE1的蛋白表达水平在免疫2、4、6次后C57BL/6J组〈Aβ3-10组〈对照组（F=432.843,P〈0.001;F=57.673,P〈0.001;F=26.550,P=0.001）,NF-κB的蛋白表达水平在免疫2次后C57BL/6J组〈Aβ3-10组〈对照组（F=109.127,P〈0.001）;免疫4,6次后Aβ3-10组〈C57BL/6J组〈对照组（F=30.301,P〈0.001;F=129.967,P〈0.001）。GFAP的蛋白表达水平在免疫2、4、6次后C57BL/6J组〈Aβ3-10组〈对照组（F=27.782,P=0.001;F=26.132,P=0.001;F=26.450,P=0.001）;Aβ1-42在脑内的分布C57BL/6J组〈Aβ3-10组〈对照组（皮质：F=5.395,P=0.021;F=47.135,P=0.000;F=25.306,P=0.000,海马：F=11.023,P=0.002;F=14.936,P=0.001;F=50.132,P=0.000）。总潜伏期C57BL/6J组〈Aβ3-10组〈对照组（F=8.938,P=0.016;F=5.745,P=0.04;F=7.073,P=0.017）。结论 Aβ3-10重复片段质粒可以影响脑内BACE1的表达,影响Aβ产生,改善空间记忆能力。

英文摘要：

Objective To explore the effects of Aβ3-10 repeat fragment plasmid immunotherapy on BACE1 in APPswe/PSEN1 double transgenic （AD） mouse brains. Method Aβ3-10 repeat fragment plasmid was used to immune 3 months APPswe/PSEN1 double transgenic mice. Equal amount of PBS was used to immune the control and C57BL/6J groups. RT-PCR method, Western blotting methods immunohistochemical method were used to detect BACE1 mRNA level, BACE1 / GFAP/NF-kB protein levels and Aβ1-42 distribution in the brain after 2, 4 and 6 immunization injections in every group, respectively. Morris water maze was used to detect the changes of behaviors. Result After two injections, the BACE1 mRNA expression levels was, in a descent order, C57BL/6J group 〈 Aβ3-10 group 〈 control group （F=4.649, P=0.021）. After four injections, the BACE1 mRNA expression levels was, in a descent order, the Aβ3-10 group 〈 C57BL/6J group 〈 control group （F=115.683, P=0.001 ）; after six injections, the BACE1 mRNA expression levels was, in a descent order, the C57BL/6J group 〈 Aβ3-10 group 〈 control group（F=86.600, P 〈 0.001）. After two, four and six injections, the protein expression level of BACE1 was C57BL/6J group 〈 Aβ3-10 group 〈 control group （F=432.843, P〈 0.001; F=57.673, P 〈 0.001; F=26.550, P=0.001 ）; the protein expression level of GFAP was C57BL/6J group 〈 Aβ3-10 group 〈 control group（F=27.782, P=0.001; F=26.132, P=0.001; F=26.450, P=0.001）; and Aβ1-42 distribution in the brain was C57BL/6J group 〈 Aβ3-10 group 〈 control group （cortex： F=5.395,P= 0.021; F= 47.135, P= 0.000; F= 25.306, P= 0.000, hippocampus： F=11.023, P= 0.002; F=14.936, P=0.001; F= 50.132, P= 0.000）. The total latent period was C57BL/6J group 〈 Aβ3-10 group 〈 control group（F=8.938, P= 0.016; F=5.745, P=0.04; F= 7.073, P= 0.017）. Conclusion Aβ3-10 repeat fragment plasmid immunotherapy can affect the expression level of BACE1 and Aβ production, improving spatial memory.