左乙拉西坦对热性惊厥大鼠治疗作用的研究

Treatment effect of levetiracetam on febrile convulsion in rats

目的观察左乙拉西坦对热性惊厥大鼠的治疗作用。方法通过热水浴建立热性惊厥大鼠模型,将40只SD幼龄热性惊厥大鼠随机分为模型组及左乙拉西坦低、中、高剂量组[100、200、300 mg/(kg·d)],分别于造模前灌胃,造模后进行47℃热水浴试验,每天惊厥1次,共惊厥5 d。观察每组大鼠惊厥潜伏期、惊厥持续时间、惊厥级别。采用TUNLE法检测各组大鼠海马神经元凋亡情况。试剂盒法检测海马组织中含半胱氨酸的天冬氨酸水解酶(Caspase 3)活性及谷氨酸(Glu)含量,Western blot检测γ-氨基丁酸(GABA蛋白)表达量。结果与模型组比较,左乙拉西坦低、中、高剂量组中大鼠惊厥潜伏期延长,惊厥持续时间缩短,惊厥严重程度降低,海马神经元凋亡率降低,Caspase 3活性及Glu含量降低,GABA表达量提高,差异均有统计学意义(P<0.01)。结论左乙拉西坦对热性惊厥大鼠具有显著治疗作用,可能与抑制神经元凋亡及调节Glu与GABA表达量有关。

Objective To explore the therapeutic effect of levetiracetam on febrile convulsion in rats.Methods The model of febrile convulsion in rats was established by hot water bath.Forty SD young febrile convulsion rats were randomly divided into model group and low,medium and high dose levetiracetam group[100 200 and 300 mg/（kg·d）].Before modeling,the rats were given intragastric administration,then received hot water bath experiment once daily for a total of five days.The rats＇ latency,seizure duration and seizure level were observed.The apoptosis of hippocampal neurons was examined by TUNEL method.The activity of cysteinyl aspartate specific proteinase 3（Caspase3） and level of glutamate（Glu） was examined.The expression of gamma aminobutyric acid（GABA） was examined by Western blot.Results Compared with model group,the convulsant latency in levetiracetam groups was prolonged（P〈0.01）,the duration of convulsion was shortened（P〈0.01）;the severity of convulsion was alleviated（P〈0.01）;the rate of apoptosis of hippocampal neurons,the activity of Caspase 3 and the level of Glu were decreased（P〈0.01）,the expression of GABA was increased（P〈0.01）.Conclusion Levetiracetam has significant therapeutic effect on febrile convulsion in rats,which is related to inhibiting of neuronal apoptosis and regulating the expression of Glu and GABA.