电针对7月龄APP/PS1双转基因鼠行为学及海马微血管壁Aβ沉积影响的研究

Effect of Electroacupuncture on Behaviours and Hippocampal Microvascular Aβ Deposition in 7-month-old APP/PSI Double Transgenic Mice

目的通过观察电针对APP/PS1双转基因小鼠海马微血管壁A?沉积及学习记忆能力的影响,探讨电针治疗阿尔茨海默病(AD)的一种作用机制,即改善A?的脑微血管清除途径。方法将24只7月龄雄性APP/PS1双转基因鼠随机分为模型组、电针治疗组,各12只,以同窝同性别的转基因阴性小鼠(12只)为空白对照组。电针治疗组电针百会、涌泉,每次15 min,隔日1次,共6星期。治疗后,以Morris水迷宫检测小鼠空间学习记忆能力,以免疫组化法检测A?1-40、A?1-42在海马脑微血管壁和老年斑的表达,使用Imagine Pro Plus软件对海马脑微血管壁A?的阳性表达进行半定量分析。结果 Morries水迷宫结果显示,与空白对照组相比,模型组逃避潜伏时延长(P<0.05);穿越平台次数及平台象限内游泳时间均减少(P<0.05)。与模型组相比,电针治疗组逃避潜伏时变短(P<0.05),穿越平台次数和平台象限内游泳时间均增加(P<0.05)。免疫组化结果显示,模型组海马微血管壁A?1-42、A?1-40积分光密度均高于空白对照组(P<0.05),且海马内出现老年斑。电针治疗组海马微血管壁A?1-42、A?1-40积分光密度均低于模型组(P<0.05)。结论电针改善了小鼠学习记忆损害,减轻了海马微血管壁A?沉积,其机制可能是通过改善A?的脑微血管清除途径,从而降低脑内A?沉积实现的。

Objective To explore one mechanism of therapeutic action of electroacupuncture on Alzheimer＇s disease（AD）,that is,improving the way to eliminate cerebral microvascular A？ by investigating the effect of electroacupuncture on hippocampal microvascular A？ deposition and learning and memory abilities in APP/PSI double transgenic mice.Method Twenty-four 7-month-old male APP/PSI double transgenic mice were randomized into model and electroacupuncture groups,12 mice each.Same sex transgene-negative littermate mice（12 mice）constituted a blank control group.The electroacupuncture group received electric acupuncture at points Baihui（GV20）and Yongquan（KI1）,15 min once every other day,for a total of six weeks.After treatment,mouse learning and memory abilities were tested using the Morris water maze.The expressions of A？ 1-40 and A？ 1-42 in the hippocampal microvascular wall and senile plaque were determined by immunohistochemical method.Hippocampal microvascular A？-positive expression was semi-quantitatively analyzed using the Imagine Pro Plus software.Result The Morris water maze test showed that escape latency lengthened（P〈0.05）,and the number of crossing platform and swimming time in the platform quadrant decreased（P〈0.05）in the model group compared with the blank control group.Escape latency shortened（P〈0.05）,and the number of crossing platform and swimming time in the platform quadrant increased（P〈0.05）in the electroacupuncture group compared with the model group.The immunohistochemical results showed that hippocampal microvascular A？ 1-42 and A？ 1-40 integral optical densities were higher in the model group than in the blank control group（P〈0.05）and senile plaques appeared in the hippocampus.Hippocampal microvascular A？ 1-42 and A？ 1-40 integral optical densities were lower in the in the electroacupuncture group than in the model group（P〈0.05）.Conclusion Electroacupuncture reduces mouse learning and memory impairments and hippocampal microvascular A？ deposition.Its mechanism may be that electroacupuncture improves the way of eliminating cerebral microvascular A？ to decrease cerebral A？ deposition.