APP/PS1双转基因小鼠CBS过表达对Aβ代谢及认知功能的影响  

Effect of cystathionine-β-synthase overexpression on amyloid-β peptide metabolism and cognitive function in APP / PS1 transgenic mice

作　　者：刘梦洁[1] 陈秋霞[1] 高丹[1] 乔沛丰 赵丰丽[1] 晏宁[2] 张华[1] 晏勇[1] 

机构地区：[1]重庆医科大学附属第一医院神经内科,重庆市神经病学重点实验室,重庆400016 [2]重庆医科大学附属大学城医院神经内科,重庆401331

出　　处：《第三军医大学学报》2015年第17期1750-1754,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81271222)~~

摘　　要：目的探讨APP/PS1双转基因小鼠胱硫醚-β-合酶(cystathionine-β-synthase,CBS)过表达对Aβ代谢及认知功能的影响。方法向APP/PS1转基因小鼠脑组织内注射慢病毒构建CBS过表达模型,以空载病毒作阴性对照。4周后行Morris水迷宫检测各组小鼠认知功能,敏感硫电极、免疫组化测定海马组织H2S、CBS、Aβ1-42含量。结果 1过表达CBS组小鼠脑组织内H2S含量显著增加(P<0.05);2过表达CBS组小鼠逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.05);3过表达CBS组小鼠脑组织内Aβ1-42含量明显降低(P<0.01),所形成老年斑的数量和大小明显减少。结论增加APP/PS1双转基因小鼠脑组织内CBS表达含量可减少Aβ1-42生成并改善小鼠认知功能。Objective To investigate the effect of cystathionine-β-synthase（ CBS） overexpression on amyloid beta peptide（ Aβ） metabolism and cognition in amyloid peptide precursor（ APP） / presenilin 1（ PS1） transgenic mice. Methods CBS overexpression lentivirus was injected into the hippocampus of APP/PS1 transgenic mice,and dummy vector lentivirus was used as negative control. After 4 weeks,cognitive function was measured by Morris water maze. The level of H2 S was tested by sensitive sulfur electrode assay.The expression and distribution of CBS and Aβ1- 42 were detected by immunohistochemical staining. Results H2 S level in the brain of the mice was significantly increased in the CBS-overexpression group（ P 0. 05）.The escape latency was shortened,and the crossing plat times were increased in the CBS overexpression group（ P 0. 05）. The level of Aβ1- 42 was decreased（ P 0. 01）,and the number and size of senile plaques were reduced in the CBS-overexpression group（ P 0. 05）. Conclusion Up-regulation of CBS can reduce the deposition of Aβ1- 42 and improve the cognitive function of APP / PS1 transgenic mice through increasing H2 S level in the brain.

关 键 词：阿尔茨海默病 硫化氢 胱硫醚-β-合酶 Β淀粉样蛋白 认知功能损害 

分 类 号：R338.64[医药卫生—人体生理学] R345[医药卫生—基础医学]