缬草酸对癫痫小鼠神经元保护及P-糖蛋白表达的影响  

Effect of valeric acid on neuronal protection and P-glycoprotein expression in epileptic mice

作　　者：于忠娟 柴峰 时宝林 张跃其[2] 吴春丽[3] YU Zhongjuan;CHAI Feng;SHI Baolin;ZHANG Yueqi;WU Chunli(Department of Internal Medicine,Sixth People’s Hospital of Weifang,Weifang 261000,China;Department of Neurology,People’s Hospital of Weifang,Weifang 261000;First Department of Obstetrics,People’s Hospital of Weifang,Weifang 261000)

机构地区：[1]山东省潍坊市第六人民医院内科,山东潍坊261000 [2]山东省潍坊市人民医院神经内科,山东潍坊261000 [3]山东省潍坊市人民医院产一科,山东潍坊261000

出　　处：《中国比较医学杂志》2020年第11期34-39,共6页Chinese Journal of Comparative Medicine

基　　金：潍坊市科技发展计划项目(2019YX072)。

摘　　要：目的研究缬草酸联合丙戊酸钠(VPA)对戊四唑(PTZ)诱导癫痫小鼠的神经元保护作用及对P-糖蛋白(P-GP)表达影响。方法将小鼠分成6组:正常对照组、模型对照组、VPA组、缬草酸组+VPA(低中高剂量各一组),记录各组癫痫发作潜伏期延长及持续时间;分析脑组织P-GP和caspase-3活性片段在脑组织中的表达及脑皮层神经元凋亡率。结果与VPA组比较,不同剂量缬草酸+VPA组发作持续时间缩短,中剂量缬草酸+VPA组发作潜伏期延长。中剂量及高剂量缬草酸+VPA组癫痫发作级别较VPA组下降。模型对照组大脑皮质P-GP明显高于正常对照组,VPA组P-GP蛋白表达较模型对照组无明显改变,缬草酸+VPA各组P-GP蛋白较VPA组下降,缬草酸中剂量组Cleaved-caspase-3表达较VPA组下降。缬草酸+VPA各组凋亡率较VPA组下降。结论缬草酸可能通过P-GP表达减少相关机制降低了戊四唑点燃/VPA处理小鼠的癫痫发作严重程度。Objective To study the protective effect of valeric acid combined with sodium valproate(VPA)on pentylenetetrazole-induced epilepsy mice and P-glycoprotein(P-GP)expression.Methods Mice were divided into six groups:normal control group,model control group,VPA group,and valeric acid+VPA group(low,medium,and high doses).The expression of P-GP and caspase-3 active fragments in brain tissue and the rate of neuronal apoptosis in the cerebral cortex were analyzed.Results Compared with the VPA group,the seizure duration in all dose valeric acid+VPA groups was shortened,and the seizure latency in the middle-dose valeric acid group was prolonged.The seizure level in the middle-dose and high-dose valeric acid groups was lower than that in the VPA group.P-GP in the cerebral cortex of the model control group was significantly higher than that of the normal control group.The expression of P-GP protein in the VPA group was not significantly different compared with the model control group.Levels of P-GP protein were decreased in all dose valeric acid+VPA groups compared with the VPA group.The expression of caspase-3 was decreased compared with the VPA group.The apoptosis rate in each dose valeric acid+VPA group was lower than that in the VPA group.Conclusions Valeric acid may reduce the severity of seizures in pentylenetetrazol ignition/VPA-treated mice through a mechanism related to reduced P-GP expression.

关 键 词：缬草酸 癫痫 丙戊酸钠 P-糖蛋白 凋亡 

分 类 号：R-33[医药卫生]