丙戊酸钠对APP/PS1双转基因小鼠脑内星形胶质细胞和神经营养因子的影响

Effect of valproic acid on astrocyte and neurotrophic factors in APP/PS1 double transgenic mice

摘要:

目的：观察丙戊酸钠（valproic acid sodium salt，VPA）对阿尔茨海默病（Alzheimer’s disease，AD）模型小鼠脑内星形胶质细胞、脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）和胶质细胞源性神经营养因子（glial cell line-derived neu－rotrophic factor，GDNF）的影响。方法：取3月龄的APP/PS1双转基因小鼠AD模型小鼠24只，按随机数字表法平均分为治疗组和对照组。VPA治疗组小鼠腹腔注射VPA 30 mg/（kg·d），对照组小鼠腹腔注射等量生理盐水，采用免疫组化学法观察2组小鼠皮质和海马区星形胶质细胞数量的变化，Western blot检测2组小鼠皮质和海马BDNF 和GDNF的表达水平。结果：与对照组比较，VPA治疗组小鼠皮质和海马区星形胶质细胞标志物胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）的阳性细胞数量均明显减少（t=5.476、8.793，P均＝0.00０），BDNF 和GDNF 表达水平均明显升高（t=4.303，P=0.001；t=2.376，P=0.032）。结论：VPA可抑制星形胶质细胞增生，提高神经营养因子的表达水平。

Abstract:

Objective：To investigate the effect of valproic acid sodium salt（VPA） on astrocyte and neurotrophic factors in the brain of APP/PS1 double transgenic mice. Methods：Alzheimer’s disease（AD） model was established with APP/PS1 double transgenic mice. Twenty-four mice（3-month-old） were randomly divided into a VPA group and a control group. The mice of VPA group and control group were intra peritoneally injected with VPA 30 mg/（kg·d） and the same amount of normal saline for 4 weeks. Immunohistochemistry staining was applied to detect the number of astrocytes，while Western blot was used to observe the expression of brain-derived neu－rotrophic factor（BDNF） and glial cell line-derived neurotrophic factor（GDNF）. Results：Compared with those of control group，the number of positive cells of the astrocyte marker glial fibrillary acidic protein（GFAP） in the cortex and hippocampus of VPA treatment mice was significantly reduced（t=5.476，8.793，P<0.001） and the expression levels of BDNF and GDNF were significantly increased（t=4.303，P=0.001；t=2.376，P=0.032）. Conclusion：VPA can inhibit the proliferation of astrocytes，enhance the expression of neu－rotrophic factors.