李学，马建军，张俊红，李六一，祁亚伟，吴少璞，李东升，杨红旗，王文霞.经鼻给予神经生长因子联合运动训练对APP/PS1转基因小鼠神经保护作用及学习记忆的影响[J].中华物理医学与康复杂志,2016,38(7):487-491
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| 经鼻给予神经生长因子联合运动训练对APP/PS1转基因小鼠神经保护作用及学习记忆的影响 |
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| DOI： |
| 中文关键词: 阿尔茨海默病 APP/PS1转基因小鼠 神经生长因子 运动 认知能力 |
| 英文关键词: Alzheimer′s disease Nerve growth factors Exercise Learning ability Memory |
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| 中文摘要: |
| 目的探讨经鼻给予神经生长因子（NGF）联合运动训练对APP/PS1转基因小鼠神经保护作用及对其学习记忆功能的影响。 方法采用随机数字表法将24只6月龄APP/PS1转基因小鼠分为对照组、NGF组、运动组及NGF联合运动训练组（简称联合组）。对照组小鼠每日给予50μl生理盐水滴鼻；NGF组小鼠每日经鼻滴入50μl含NGF（0.1mg/ml）生理盐水溶液；运动组小鼠每日给予50μl生理盐水滴鼻，同时辅以小强度跑台运动，每次持续训练30min；联合组小鼠每日8∶00经鼻滴入50μl含NGF（0.1mg/ml）生理盐水溶液，下午14∶00辅以小强度跑台运动，持续训练30min。采用Morris水迷宫检测各组小鼠学习记忆能力变化；于实验进行21d时取各组小鼠脑标本进行免疫组化染色，观察大脑皮质APP、Ki-67及海马区NeuN阳性细胞表达情况。 结果Morris水迷宫定向航行实验中4组小鼠找到平台的潜伏期组间差异具有统计学意义（P<0.05），其中NGF组、运动组及联合组潜伏期分别为（21.8±5.9）s、（20.2±5.6）s、（12.3±4.2）s，均明显短于对照组水平［（30.7±9.6）s］，并且联合组潜伏期亦显著短于NGF组及运动组（P<0.05）；空间探索实验中各组小鼠目标象限时间百分比组间差异具有统计学意义（P<0.05），其中联合组目标象限时间百分比［（36.3±6.6）%］明显大于NGF组［（27.1±11.9）%］及运动组［（26.7±8.5）%］，组间差异具有统计学意义（P<0.05）。免疫组化检查结果显示，联合组与其他3组比较，其神经元排列整齐、细胞致密，APP蛋白表达明显减弱，Ki-67及NeuN阳性细胞表达均显著增强。 结论NGF滴鼻联合运动训练能显著提高APP/PS1转基因小鼠空间学习及记忆能力，其治疗机制可能与抑制APP表达、减少神经元损伤、促进内源性神经细胞增殖及存活有关。 |
| 英文摘要: |
| Objective To investigate the effect of nerve growth factor (NGF) combined with exercise training on nerve protection, learning and memory. MethodsTwenty-four six-month-old APP/PS1 mice were randomly divided into a control group, an NGF group, an exercise group and an NGF combined with exercise training group (the combined group), each of 6. The control group mice were given 50 μL of saline intra-nasally every day, while the NGF group were given 50 μL of NGF solution (0.1 mg/ml) intranasally. The exercise group was given 50 μL of saline intra-nasally plus 30 minutes of treadmill exercise daily, while the combined group was given 50 μL of the NGF solution and 30 minutes of exercise. The intervention lasted 21 days. Then Morris water maze test was conducted to evaluate the memory of all groups, and all of the mice were sacrificed and immunohistochemical staining was used to check the levels of APP, Ki-67 expression in cortex and NeuN expression in hippocampus. Results In the place navigation test, significant differences in escape latency were observed among the 4 groups, with the NGF, exercise and combined groups showing average latencies significantly shorter than that of the control group The average latency of the combined group was also significantly shorter than that of the NGF and exercise groups. In the spatial probe, there were significant differences among the 4 groups in the percentage of time spent in the target quadrant. The combined group′s average was significantly larger than those of the NGF and exercises groups. The immunochemistry showed that the combined group had better-arranged neurons and more cells compared with the 3 other groups. The average APP protein expression of the combined group was significantly lower than that of the other groups, but their Ki-67-positive and NeuN-positive cells were found to be significantly more numerous. Conclusion NGF combined with exercise can improve learning and memory, at least in APP/ PS1 mice. This might be associated with its reducing the expression of APP and promoting the expression of Ki-67 and NeuN. |
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