【摘要】 背景:神经干细胞能够在体外持续扩增,具有较强的增殖能力和较强的可塑性,能够在成年宿主中枢神经系统中存活、迁移、分化以及与宿主组织整合较好。目的:分析神经干细胞移植对侧脑室注射192-IgG-saporin老年性阿尔茨海默病模型鼠基底前脑神经元p75NGFR阳性神经元和行为学的影响。方法:24只SD大鼠随机数字表法均分为3组:对照组、模型组、移植组。10只新生SD鼠(<24h)用于神经干细胞分离培养。模型组及移植组192-IgG-saporin侧脑室注射SD大鼠建立阿尔茨海默病模型。造模后,移植组行基底前脑神经干细胞移植。4周后行Y迷宫检测,结合图像分析技术观察大鼠基底前脑p75NGFR阳性神经元数目和形态学参数的变化。结果与结论:注射192-IgG-saporin1个月,模型组损伤侧基底前脑内侧隔核和斜角带垂直支p75NGFR阳性神经元数明显减少(P<0.01),移植组分别恢复到对照组的74.85%和71.66%,与模型组损伤侧相比较,差异显著(P<0.01)。Y迷宫测试结果显示,移植组大鼠的空间学习能力和记忆能力有改善(P<0.05),基底前脑p75NGFR阳性神经元细胞数与大鼠的空间学习记忆能力呈正相关。提示,神经干细胞移植对注射192-IgG-saporin致阿尔茨海默病鼠基底前脑胆碱能神经元有明显的补充和保护作用,可改善大鼠的学习记忆能力。更多还原

【Abstract】 BACKGROUND:Neural stem cells(NSCs) can have a continuous amplification in vitro,have the reproductive activity and plasticity and can survive,migrate,differentiate and integrate into host central nervous system in adult life.OBJECTIVE:To analyze the effects of NSCs transplantation on the cholinergic p75NGFR positive neurons and behavior of the basal forebrain and behavior of the rat model of Alzheimer’s disease(AD) with lateral ventricle injection of 192-IgG-saporin.METHODS:A total of 24 Sprague Dawley rats were randomly divided into three groups:normal group,model group and transplantation group.A total of 10 new born Sprague Dawley mouse(< 24 hours) were used for isolation and culture of NSCs.192-IgG-saporin was injected into the lateral ventricle of Sprague Dawley rats to establish AD animal model.Then,NSCs were transplanted in basal forebrain in the transplantation group.At four weeks,Y-maze test was performed.The changes of morphologic data and number of p75NGFR positive neurons were measured in basal forebrain by using image analysis.RESULTS AND CONCLUSION:About 1 month after 192-IgG-saporin injection,the number of p75NGFR-positive neurons at the lesion side of medial septal nucleus and vertical diagonal branch was significantly reduced in the model group(P < 0.01).However,the number of p75NGFR-positive neurons at the lesion side of medial septal nucleus and vertical diagonal branch was increased up to 74.85% and 71.66% in the transplantation group,and there were significant differences compared with the model group(P < 0.01).Y-maze test showed the abilities of learning and memory of transplantation group were improved(P < 0.05).The effects of learning and memory may be positively related with the number of p75NGFR neurons of the basal forebrain.These indicated that NSCs transplantation is effective in improving ability of learning and memory and can improve and protect p75NGFR positive neurons of the basal forebrain in 192-IgG-saporin-induced AD models.更多还原