人脑源性神经营养因子基因修饰神经干细胞移植对痴呆大鼠学习记忆的改善

目的　观察神经干细胞( neural stem cell,NSC)和人脑源性神经营养因子( human brain derivedneurotrophic factor,h BDNF)基因修饰NSC移植对阿尔茨海默病( Alzheimer disease,AD)模型鼠的学习记忆改善作用。　方法　SD大鼠4 0只随机分为4组,每组10只。 组为正常对照组;其余3组进行单侧切断大鼠穹窿海马伞( fibria-fornix,FF)制备AD模型, 组为损伤组; 、组于术后10～12 d,侧脑室移植h BDNF基因修饰及未修饰的NSC分别为NSC组和BDNF组。移植后2周进行Morris水迷宫定位航行及空间探索行为学检测。　结果　 组和 组的平均逃避潜伏期为4 1.84±2 1.76 s和2 5 .2 3±17.0 6 s,较 组潜伏期70 .91±2 3.6 7s明显缩短,差异有统计学意义( P<0 .0 1) ;平台象限游泳距离占总游泳距离的百分比: 组和 组分别为36 .9%和4 2 .0 % ,较 组2 6 .0 %明显增高,差异有统计学意义( P<0 .0 1) ; 组大鼠采取边缘式和随机式搜索模式显著多于其它各组,差异有统计学意义( P<0 .0 1)。其中 组大鼠的平均逃避潜伏期和平台象限游泳距离百分比及搜索策略接近 组( P>0 .0 5 ) ,采取直线式和趋向式的搜索策略显著多于其它各组( P<0 .0 1)。　结论　NSC和h BDNF基因修饰NSC移植对AD模型鼠的行为学有不同程度的改善,h BDNF基因修饰NSC移植较

LEARNING AND MEMORY AMELIORATION OF TRANSPLANTATION OF THE NEURAL STEM CELLS MODIFIED WITH HUMAN BRAIN-DERIVED NEUROTROPHIC FACTOR GENE ON ALZHEIMER DISEASE MODEL RAT

OBJECTIVE: To investigate the memory amelioration of the Alzheimer disease (AD) model rat after being transplanted the single neural stem cells (NSC) and NSC modified with human brain-derived neurotrophic factor (hBDNF) gene. METHODS: Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group III and group IV respectively. Two weeks after transplantation, the amelioration of memory impairment of the rats was detected by Morris water maze. RESULTS: The average escaping latency of the group III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter than that of the group II (70.91 +/- 23.67 s) (P<0.01). The percentage of swimming distance in the platform quadrant in group III (36.9%) and in group IV (42.0%) was higher than that in the group II (26.0%) (P<0.01). More marginal and random strategies were used in group II. The percentage of swimming distance in the platform quadrant in group IV was also greater than that in group III (P<0.05). There were no significant differences in the average escaping latency, the percentage of swimming distance in the platform quadrant and the probe strategy between group IV and group I (P>0.05). More lineal and oriented strategies were used in group IV. CONCLUSION: The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the group III.