PGC-1α基因缺失对β-淀粉样蛋白诱导小鼠神经毒性的影响  

Effect of PGC-1αknockout on the neurotoxicity induced byβ-amyloid in mice

作　　者：孙治坤[1] 马兴荣[2] 陈帅[1] 贺爽[1] 张杰文[1] SUN Zhikun;MA Xingrong;CHEN Shuai;HE Shuang;ZHANG Jiewen(Henan Provincial People’s Hospital,Zhengzhou 450003,China;The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]河南省人民医院,河南郑州450003 [2]郑州大学第一附属医院,河南郑州450052

出　　处：《中国实用神经疾病杂志》2020年第23期2025-2031,共7页Chinese Journal of Practical Nervous Diseases

基　　金：国家自然科学基金资助项目(编号:81873727)。

摘　　要：目的观察PGC-1α基因缺失对β-淀粉样蛋白诱导的小鼠神经毒性的影响。方法健康雄性PGC-1α基因敲除小鼠和C57BL16小鼠各12只,常规饲养3 d后按照随机化原则将两种基因型组小鼠分为对照组和Aβ注射组,每组6只。在脑立体定位仪指导下把凝聚态Aβ1-40注射到不同基因组(正常基因和PGC-1α基因敲除)小鼠的双侧侧脑室中,然后采用Morris水迷宫评估小鼠的学习记忆能力,检测各组研究对象脑皮质和海马组织内ChAT和AchE以及氧化应激相关指标。结果Aβ1-40注射双侧侧脑室后,两种不同基因组小鼠的学习记忆能力与同种基因型小鼠对照组相比均明显降低(P<0.05),脑皮质和海马组织内ChAT活性均明显降低(P<0.05),AchE活性均明显升高(P<0.05),SOD及GSH的活性均明显降低(P<0.05),而MDA的活性均明显升高(P<0.05);与正常基因小鼠相比,PGC-1α基因敲除组小鼠侧脑室注射Aβ1-40后较正常基因组小鼠的学习记忆水平明显下降(P<0.05),同时脑皮质和海马组织内ChAT活性明显降低(P<0.05),AchE活性明显升高(P<0.05),SOD及GSH的活性均明显降低(P<0.05),而MDA的活性明显升高(P<0.05)。结论PGC-1α基因敲除可增强Aβ诱导的神经毒性作用。Objective To investigate the effect of PGC-1αknockout on memory impairment and oxidative stress in mice induced byβ-amyloid.Methodsβ-amyloid 1-40 was injected into the bilateral lateral ventricles of mice with different genomes(normal gene and PGC-1αgene knockout).The Morris water maze was used to evaluate the spatial learning and memory ability.In cortex and hippocampus of the mice,we detected the changes of acetylcholinesterase,choline acetyltransferase and oxidative stress related indexes,such as superoxide dismutase,glutathione and malondialdehydein,and so on.Results Compared with normal genome mice,all the changes induced byβ-amyloid including the memory impairment,the changes of acetylcholinesterase and choline acetyltransferase activity and the oxidative stress reaction all aggravated in the PGC-1αknockout mice(P<0.05).Conclusion PGC-1αknockout can aggravated the neurotoxicity induced byβ-amyloid.

关 键 词：阿尔茨海默病 PGC-1Α Β-淀粉样蛋白 氧化应激 认知功能障碍 痴呆 

分 类 号：R749.16[医药卫生—神经病学与精神病学]