下调GABA受体基因对癫痫模型大鼠海马神经细胞凋亡的影响及作用机制  

The effect of down-regulation of GABA receptor gene on neuronal apoptosis in hippocampus of epileptic rats and its mechanism

作　　者：李萍[1] 黄晓松[1] 黄远桃[1] 易艳辉[1] Li Ping;Huang Xiaosong;Huang Yuanpeach(Department of Neurology,Brain Hospital of Hunan province,Changsha 410007)

机构地区：[1]湖南省脑科医院神经内科,长沙410007

出　　处：《卒中与神经疾病》2020年第3期298-303,共6页Stroke and Nervous Diseases

基　　金：湖南省自然科学基金资助项目(2017JJ3231)。

摘　　要：目的探讨下调GABA受体基因对癫痫模型大鼠海马神经细胞凋亡的影响及作用机制。方法选择30只SD健康雄性大鼠,建立癫痫模型,建模成功后分为模型组、上调组、下调组各10只;进行细胞转染建立稳定转染的GABA上调组、GABA下调组;检测3组大鼠海马神经细胞凋亡及PI3K、AKt、mTOR、Bax、Caspase-3蛋白表达水平。结果上调组大鼠各时间点海马神经细胞凋亡率高于模型组(P<0.05);下调组大鼠各时间点海马神经细胞凋亡率低于模型组(P<0.05);下调组大鼠各时间点海马神经细胞凋亡率低于上调组(P<0.05)。上调组大鼠各时间点海马神经细胞增殖率、Bcl-2、p-PI3K、p-AKt、p-mTOR蛋白表达水平均低于模型组,而Bax、Caspase-3蛋白表达水平高于模型组(P<0.05);下调组大鼠各时间点海马神经细胞增殖率、Bcl-2、p-PI3K、p-AKt、p-mTOR蛋白表达水平均高于模型组,而Bax、Caspase-3蛋白表达水平低于模型组(P<0.05);下调组大鼠各时间点海马神经细胞增值率、Bcl-2、p-PI3K、p-AKt、p-mTOR蛋白表达水平均高于上调组,而Bax、Caspase-3蛋白表达水平低于上调组(P<0.05)。结论下调GABA受体基因可能是通过调节PI3K/AKt/mTOR来作用于下游凋亡靶基因,最终抑制癫痫模型大鼠海马神经细胞凋亡。Objective To study the effect of down-regulation of GABA receptor gene on neuronal apoptosis in hippocampus of epileptic rats and its mechanism.Methods Thirty healthy male SD rats were selected to establish epilepsy model. After successful modeling, they were divided into model group, up-regulation group and down-regulation group, 10 rats in each group. Cell transfection was carried out to establish stable GABA up-regulation group and GABA down-regulation group. The apoptotic rate of hippocampal nerve cells and the expression levels of PI3 K, AKt, mTOR, Bax and Caspase-3 protein in hippocampal were detected and compared among three groups.Results The apoptotic rate of hippocampal neurons in the up-regulated group was higher than that in the model group at each time point(P<0.05).The expression levels of Bcl-2, p-PI3 K, p-AKt and p-mTOR proteins in hippocampus of up-regulated group were lower than those of model group at each time point, and the expression levels of Bax and Caspase-3 proteins was higher than those of model group(P<0.05),the proliferation rate of hippocampal neurons, expression levels of Bcl-2, p-PI3 K, p-AKt and p-mTOR proteins of down-regulated group were higher than those of model group(P<0.05). The expression levels of Bax and Caspase-3 proteins were lower than those of model group(P<0.05), proliferation rate of hippocampal neuron cell, the expression levels of Bcl-2, p-PI3 K, p-AKt, p-mTOR protein in down-regulated group was higher than those in up-regulated group at each time point, and the expression levels of Bax and Caspase-3 proteins was higher than those in up-regulated group(P<0.05).Conclusion Down-regulation of GABA receptor gene acted on downstream apoptotic target genes by regulating PI3 K/AKt/mTOR, and ultimately inhibited hippocampal neuronal apoptosis in epileptic model rats.

关 键 词：海马 神经元 凋亡 癫痫 

分 类 号：R74[医药卫生—神经病学与精神病学]