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目的:观察拉莫三嗪对γ-羟丁酸(GHB)致失神发作大鼠脑电及脑内超极化激活环核苷酸门控阳离子通道(HCN)的亚型HCN1、HCN2表达变化的影响,探讨拉莫三嗪抗失神癫痫的可能作用机制。方法:健康成年雄性SD大鼠,随机分为空白对照组,模型组,拉莫三嗪治疗组(低剂量组为8 mg/(kg·d)、中剂量组为12 mg/(kg·d)、高剂量组为24 mg/(kg·d)),每组7只。空白对照组及模型组每日应用0.25%的甲基纤维素钠溶液灌胃,治疗组每日应用0.25%的甲基纤维素钠溶液配制的浓度为2 mg/mL的拉莫三嗪混悬液灌胃。手术埋置皮层脑电电极。腹腔注射GHB的前体γ-丁内酯(GBL)200 mg/kg制作大鼠失神发作模型,并监测脑电。免疫组化法检测皮层HCN1及丘脑HCN2的表达。结果:皮层脑电图拉莫三嗪治疗组比模型组失神发作的潜伏期延长,最高波幅降低(P<0.05)。模型组皮质HCN1比空白对照组表达减少,而拉莫三嗪高、中剂量组皮质HCN1比模型组表达增加(P<0.05)。模型组丘脑HCN2表达减少,与空白对照组及治疗组相比,差异有统计学意义。结论:拉莫三嗪可以改善GHB致失神发作模型脑电图的异常表现;拉莫三嗪抗失神癫痫作用可能与调节HCN表达有关。
OBJECTIVE: To observe the changes of the expression of HCN1 and HCN2 subtypes in the brain electrical and brain hyperpolarization-activated cyclic nucleotide gated cation channels (HCN) induced by lamotrigine in GABA rat induced by GHB Influence, to explore the possible mechanism of lamotrigine anti-absence epilepsy. Methods: Healthy adult male Sprague-Dawley rats were randomly divided into blank control group, model group and lamotrigine treatment group (8 mg / (kg · d) for low dose group and 12 mg / (kg · d) for middle dose group) ), High-dose group was 24 mg / (kg · d)), 7 in each group. The blank control group and the model group were orally administered 0.25% sodium methylcellulose daily. The treatment group was treated daily with 0.25% methylcellulose sodium solution and lamotrigine at a concentration of 2 mg / mL Liquid gavage. Surgical implantation of cortical electrodes. Abdominal injection of γ-butyrolactone (GBL), a precursor of GHB, at 200 mg / kg was used to make a rat absence seizure model and EEG was monitored. Immunohistochemistry was used to detect the expression of HCN1 in the cortex and HCN2 in the thalamus. Results: The latencies of lamotrigine in cortical electroencephalogram lamotrigine treatment group were longer than those in model group, and the maximum amplitude was decreased (P <0.05). The expression of cortical HCN1 in model group was lower than that in blank control group, while the expression of HCN1 in cortex HCN1 of high and medium dose lamotrigine groups was higher than that of model group (P <0.05). The expression of HCN2 in the hypothalamus of model group decreased compared with the blank control group and the treatment group, the difference was statistically significant. CONCLUSION: Lamotrigine can improve the abnormality of EEG in GHB-induced dementia. The anti-delaying epilepsy of Lamotrigine may be related to the regulation of HCN expression.