缬草酸对癫痫小鼠神经元保护及 P-糖蛋白表达的影响
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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

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R-33

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Effect of valeric acid on neuronal protection and P-glycoprotein expression in epileptic mice
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1.Department of Internal Medicine, Sixth People’s Hospital of Weifang, Weifang 261000, China. 2. Department of Neurology, People’s Hospital of Weifang, Weifang 261000. 3. First Department of Obstetrics, People’s Hospital of Weifang, Weifang 261000

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    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。

    Abstract:

    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.

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于忠娟,柴 峰,时宝林,张跃其,吴春丽.缬草酸对癫痫小鼠神经元保护及 P-糖蛋白表达的影响[J].中国比较医学杂志,2020,30(11):34~39.

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  • 收稿日期:2020-04-21
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  • 在线发布日期: 2020-12-25
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