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目的研究丙戊酸钠(valproic acid,VPA)对APP/PS1双转基因阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠自主活动及脑组织形态结构的影响,探讨VPA对AD的保护作用及可能机制。方法将3月龄APP/PS1双转基因小鼠及同窝野生型小鼠分为VPA处理组和生理盐水对照组,运用VPA[30 mg/(kg.d)]和等量生理盐水腹腔注射4周。旷场实验观察各组小鼠的自主活动能力;尼氏染色、透射电镜观察各组小鼠脑组织的病理改变。结果行为学结果显示:与野生型小鼠相比,AD模型小鼠自主活动明显减少(P<0.05);野生型小鼠VPA处理组与对照组自主活动无明显差异(P>0.05);而AD模型小鼠VPA处理组比对照组的自主活动明显减少(P<0.05)。尼氏染色显示:AD模型小鼠脑内神经元密度显著低于野生型小鼠。AD模型小鼠中,对照组脑内神经细胞明显肿胀,尼氏小体明显减少而致细胞质淡染,神经细胞密度降低(85.2±13.3);而VPA处理组脑内神经元肿胀程度明显减轻,神经元数量显著回升(116.9±16.2,P<0.05),但VPA不影响野生型小鼠脑内的神经元数量及形态(VPA处理组:142.2±24.4 vs生理盐水对照组:136.7±23.1,P>0.05)。电镜结果显示AD模型小鼠对照组脑内神经元细胞核、线粒体及神经毡肿胀明显,突触结构稀松;而AD模型小鼠VPA处理组脑内神经元细胞核、线粒体及神经毡的水肿明显减轻,突触结构清晰。结论 VPA可显著减少APP/PS1双转基因AD模型小鼠的自主行为,显著减轻躁狂症状;VPA可改善APP/PS1双转基因小鼠脑内神经细胞的形态结构,减少肿胀的神经元并抑制神经元数量的减少。
Objective To investigate the effects of valproic acid (VPA) on autonomic activity and brain morphological structure of APP / PS1 double transgenic Alzheimer’s disease (AD) mice and to explore the protective effect of VPA on AD and Possible mechanism. Methods Three-month-old APP / PS1 transgenic mice and wild-type littermates were divided into VPA group and saline control group. VPA [30 mg / (kg · d) week. The open field experiment was used to observe the autonomic activity of mice in each group. The pathological changes of brain tissue in each group were observed by Nissl staining and transmission electron microscope. Results The behavioral results showed that compared with wild-type mice, autonomic activity was significantly decreased in AD model mice (P <0.05). There was no significant difference in autonomic activity between VPA-treated group and control group (P> 0.05) AD model mice VPA-treated group than in the control group decreased significantly (P <0.05). Nissl staining showed that the neuronal density in brain of AD model mice was significantly lower than that of wild type mice. AD model mice, the control group brain cells were significantly swollen, Nissl body significantly reduced cytoplasm caused by light staining, decreased density of nerve cells (85.2 ± 13.3); while VPA-treated group of neurons swelling significantly reduced, (116.9 ± 16.2, P <0.05). However, VPA did not affect the number and morphology of neurons in the wild-type mice (VPA-treated group: 142.2 ± 24.4 versus saline control group: 136.7 ± 23.1, P > 0.05). Electron microscopy showed that the AD model mice had obvious swelling in the nucleus, mitochondria and neurofilament of the neurons in the control group, and the synaptic structure was very loose. However, the edema of neurons, mitochondria and neurofilament in the VP model group was significantly reduced, Synapse structure is clear. Conclusions VPA can significantly reduce the autonomic behavior of APP / PS1 double transgenic AD model mice and significantly reduce the symptoms of mania. VPA can improve the morphological structure of neurons in APP / PS1 double transgenic mice brain, reduce the swelling of neurons and inhibit the nerve Decrease in the number of elements.