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目的:探讨阿尔茨海默病(Alzheimer's disease,AD)中,淀粉样前体蛋白(amyloid precursor protein,APP)在电压门控性钠离子通道2B (sodium channel-voltage-gated-beta 2B,SCN2B)介导的学习记忆认知功能改善中可能发挥的作用。方法:将SCN2B基因敲除小鼠(SCN2Bn -/-)与APP基因敲除小鼠(APPn -/-)、APP基因杂合子(APPn +/-)以及APP基因过表达小鼠(APPn +/+)配对杂交,用PCR基因检测技术对同窝小鼠尾组织进行基因分型,分为SCN2Bn -/-APPn -/-组,SCN2Bn -/-APPn +/-组以及SCN2Bn -/-APPn +/+组,C57BL/6野生型小鼠则为野生型(wild type,WT)组,每组9只。并将6月龄、12月龄、18月龄的SCN2Bn -/-APPn -/-、SCN2Bn -/- APPn +/-、SCN2Bn -/-APPn +/+转基因小鼠和同龄野生型小鼠进行Morris水迷宫与Y迷宫行为学实验来检测每组之间的认知功能;取6、12、18月龄SCN2Bn -/-APPn -/-、SCN2Bn -/- APPn +/-、SCN2Bn -/-APPn +/+的三种转基因小鼠和同龄野生型小鼠进行海马CA1区神经元突起的检测,同时对海马CA1区神经元的基底及远端突起数量进行定量分析。采用SPSS 21.0统计软件进行数据统计和分析。两组之间的差异用独立样本n t检验比较分析,多组间比较用单因素方差分析,行为学实验结果使用重复测量方差分析进行统计。n 结果:(1)水迷宫实验数据使用重复测量方差分析,数据显示18月龄小鼠中逃避潜伏期的组别和时间交互效应显著(n F时间×组别=3.63,n P<0.01)。简单效应分析发现18月龄小鼠中,与SCN2Bn -/-APPn +/-组和SCN2Bn -/-APPn -/-组小鼠比较,SCN2Bn -/-APPn +/+组小鼠第4~6天的逃避潜伏期明显延长[第4天:(47.00±2.00)s,(43.11±1.96) s,(41.89±3.06)s,n t=-4.16,1.00,均n P<0.05;第5天:(45.22±2.54) s,(36.33±2.78) s,(37.00±2.45)s,n t= -7.08,-0.54,均n P<0.05;第6天:(38.11±2.03)s,(34.11±2.32)s,(33.00±2.91)s,n t=-3.90,0.90,均n P<0.05。],目标象限停留时间缩短[(18.00±1.73)s,(25.56±1.33)s,(24.33±1.94)s;n t=10.37,1.56,均n P<0.05]。(2)Y-迷宫结果显示,与SCN2Bn -/-APPn -/-组和SCN2Bn -/-APPn +/-组小鼠比较,18月龄SCN2Bn -/-APPn +/+组小鼠新颖臂进入次数减少[(50.22±3.68)次,(57.22±3.74)次,(58.44±5.14)次;n t=3.40,-0.48,均n P<0.05],在新颖臂内停留时间减少[(10.89±0.62)min,(14.33±0.59)min,(13.89±0.74)min;n t=8.16,0.44,均n P<0.05]、在新颖臂活动距离明显减少[(37.26±2.01)m ,(45.67±2.45)m,(46.11±3.27)m ;n t=7.81,0.91,均n P<0.05]。(3)Golgi染色结果显示,与SCN2Bn -/- APPn -/-组和SCN2Bn -/-APP n +/-组小鼠比较,18月龄SCN2Bn -/-APP n +/+组小鼠海马神经元的顶端树突数量[顶端树突数量:(1.78±0.37)个,(3.67±0.81)个,(3.00±1.21)个;n t=3.36,1.41,均n P<0.05]和基底树突数量[基底树突数量:(1.11±0.50)个,(3.11±0.50)个,(2.56±0.69)个;n t=4.06,1.21,均n P<0.05]均显著减少。n 结论:SCN2B敲低可以改善老年小鼠的空间学习记忆能力,而过表达APP可以部分抵消SCN2B敲低引起的小鼠认知功能改善,其机制可能是通过影响小鼠海马CA1区神经元基底及远端的突起数量而发挥作用的。“,”Objective:To explore the potential role of amyloid precursor protein (APP) in the sodium-channel-voltage-beta 2B (SCN2B)-mediated improvement of memory and cognitive function in Alzheimer's Disease (AD).Methods:The SCN2B gene knockout mice (SCN2Bn -/-) were hybridized with APP gene knockout mice (APPn -/-), APP gene heterozygous mice (APPn +/-) and APP gene transgenic mice (APPn +/+), and the tail tissue of the same mouse was genotyped by PCR gene detection.The mice were divided into SCN2Bn -/-APPn -/- group, SCN2Bn -/-APPn +/- group and SCN2Bn -/-APPn +/+ group.The C57BL/6 wild-type mice were Wild type (WT) group, with 9 mice in each group.SCN2Bn -/-APPn -/-, SCN2Bn -/-APPn +/-, SCN2Bn -/-APPn +/+ transgenic mice and the wild-type mice at the age of 6 months, 12 months, and 18 months were tested by Morris water Maze and Y maze test to detect the cognitive function between each group.Meanwhile, SCN2Bn -/-APPn -/-, SCN2Bn -/-APPn +/-, SCN2Bn -/-APPn +/+ transgenic mice aged 6, 12, 18 months and age-match wild-type were selected to detect neuronal processes in hippocampal CA1 region, and the number of neuronal processes in basal and distal regions of hippocampal CA1 region was quantitatively analyzed.SPSS 21.0 statistical software was used for data statistics and analysis.The differences between the two groups were compared and analyzed by independent-sample n t test, the comparison between multiple groups was analyzed by one way analysis of variance (ANOVA), and repeated measurement ANOVA was used to analyze behavioral deta.n Results:Repeated measurement ANOVA was used to analyze the data of water maze test. The data showed that the interaction effect of escape latency group and time was significant in 18 month old mice (n Ftime×group=3.63, n P<0.01). Simple effect analysis showed that compared with SCN2Bn -/-APPn +/- group and SCN2Bn -/-APPn -/-group, the escape latency of mice in SCN2Bn -/-APPn +/+ group was significantly prolonged from day 4 to 6 (4th day: (47.00±2.00)s, (43.11±1.96) s, (41.89±3.06)s, n t=-4.16, 1.00, both n P<0.05; 5th day: (45.22±2.54) s, (36.33±2.78) s, (37.00±2.45)s,n t=-7.08, -0.54, both n P<0.05; 6th day: (38.11±2.03)s, (34.11±2.32)s, (33.00±2.91)s,n t=-3.90, 0.90, both n P<0.05). The residence time in the target quadrant was shortened((18.00±1.73)s, (25.56±1.33)s, (24.33 ±1.94)s;n t=10.37, 1.56, both n P<0.05). (2) Y-maze results showed that compared with SCN2Bn -/-APPn +/- group and SCN2Bn -/-APPn -/-group, the number of novel arm entry in 18 month old mice in SCN2Bn -/-APPn +/+ group was decreased((50.22±3.68), (57.22±3.74), (58. 44±5.14) ; n t=3.40, -0.48, both n P<0.05), and the residence time of stay in the new arm was reduced((10.89±0.62)min, (14.33±0.59)min, (13.89±0.74)min;n t= 8.16, 0.44, both n P<0.05), and the distance of movement in the new arm was significantly reduced ((37.26±2.01)m , (45.67±2.45)m , (46.11±3.27)m ;n t=7.81, 0.91, both n P<0.05). (3) Golgi staining showed that SCN2Bn -/-APPn +/- group and SCN2Bn -/-APPn -/-group, the number of apical dendrites in hippocampal neurons of 18 month old mice in SCN2b n -/-Appn +/+ group(number of apical dendrites: (1.78±0.37), (3.67±0.81), (3.00±1.21); n t=3.36, 1.41, both n P<0.05) and the number of basal dendrites (the number of basal dendrites: (1.11±0.50), (3.11±0.50), (2.56±0.69);n t=4.06, 1.21, both n P<0.05).n Conclusion:SCN2B knockdown can improve the ability of spatial learning and memory in aged mice.Overexpression of APP can partially offset the improvement of cognitive function caused by SCN2B knockdown, and may be affected by the number of basal and distal processes of neurons in the hippocampal CA1 region of the mice.