APPPS1双转基因小鼠CBS过表达对Aβ代谢及认知功能的影响.docVIP

APP/PS1双转基因小鼠CBS过表达对Aβ代谢及认知功能的影响 刘梦洁1，陈秋霞1，高 丹1，乔沛丰1，赵丰丽1，晏 宁2，张 华1，晏 勇1*（400016重庆，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1，附属大学城医院2） [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（p0.05）；②过表达CBS组小鼠逃避潜伏期缩短(p0.05)，穿越平台次数增加(p0.05)；③过表达CBS组小鼠脑组织内Aβ1-42含量明显降低（p0.01）， 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含量可减少Aβ1-42生成并改善小鼠认知功能。 [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 [中图法分类号] R741.05 [文献标识码] A Effects of CBS Overexpression on Metabolism of Aβ and Cognition in APP/PS1 Transgenic Mouse Liu Mengjie, Chen Qiuxia, Gao Dan, Qiao Feifeng, Yan Yong (Department of Neurology,First Affiliated Hospital,Chongqing Medical University,Chongqing,400016,China ) [Abstract] Objective The aim of this study is to investigate the effect of cystathionine-β-synthase(CBS) overexpression on Aβ metabolism and cognition changes in APP/PS1 transgenic mouse. Methods CBS overexpression lentivirus were injected into the APP/PS1 transgenic mice hippocampus, dummy vector lentivirus as negative control. After 4 weeks, cognitive function were measured by Morris water maze, the level of H2S were texted by sensitive sulfur electrode assay, the expression and distribution of CBS and Aβ1-42 were detected through immunohistochemical staining. Results ①H2S level in mice brain is effectively increased in CBS-overexpression group (p0.05); ②The escape latency is shorted and the crossing plat times is increased in CBS- overexpression group(p0.05); ③The level of Aβ1-42 is decreased(p0.01) and the number and size of senile plaques which compound by Aβ1-42 is reduced in CBS-overexpression group (p0.05). Conclusion Upregulating of CBS can reduce the deposition of Aβ1-42 and improve the cognitive founction of APP/PS1 transgenic mouse, and this behavior change could be achieved by increasing H2S levels in the brain [Key words]