NO介质在大鼠红藻氨酸诱导癫痫发作中的作用

目的：进一步探讨脑内一氧化氮(NO)介质(NO或NO衍生物)在复杂部分性及全身强直阵挛性癫痫发作中的作用。方法：采用红藻氨酸(KA)诱导大鼠癫痫发作,以NO合酶抑制剂L-硝基精氨酸(L-NNA)或NO前体L-精氨酸(L-Arg)予以预处理,观察其癫痫发作行为及海马结构内NO含量(NO2^-/NO3^-)的变化。结果：给予大鼠惊厥剂量KA(10mg/kg),15min时出现湿狗样抖动(WDS),1～3h出现全身痉挛;经L-NNA(50mg/kg)或L-Arg(40mg/kg)预处理的大鼠,注射相同剂量的KA后,其癫痫行为发生明显变化,L-NNA预处理的大鼠癫痫发作行为明显加重,表现为全身痉挛的潜伏期缩短、时间延长、死亡率提高;L-Arg预处理的大鼠癫痫发作行为减弱,WDS和全身痉挛的潜伏期均延长,发作程度减轻、时间缩短,观察时间内无一例死亡。KA给药后30min海马结构内的NO2^-/NO3^-含量迅速增多,7d时仍持续增高;与NS预处理组相比,经L-Arg预处理的动物,KA给药后3h及3d,其NO2^-/NO3^-浓度升高明显。结论：兴奋诱导性癫痫发作过程中内源性NO介质的变化可能具有重要的抗发作作用。

Effect of no mediator on kainic acid induced behavioral seizures in rats

Aim:To further explore the roles of endogenous nitric oxide (NO) or NO derivatives in complex partial seizures and generalized convulsions. Methods: The effect of pretreatment with L-nitroarginine(L-NNA), an inhibitor of nitric oxide synthase (NOS), or L-arginine(L-Arg), a precursor of NO on kainic acid (KA)-induced seizure in rats and the changes in the concentration of NO 2-/NO 3- in the hippocampus were determined. Results: The rats appeared with wet dog shakes (WDS) at 15 min and then occurred generalized convulsions during 1h to 3 h after administration of KA (10 mg/kg i.p.). However, the pretreatment of L-NNA (50 mg/kg) so dramatically promoted and enhanced KA-induced behavioral seizures that the latency of generalized convulsion was shorten dramatically, and the mortality was greatly high. In contrast, the pretreatment with L-Arg (40 mg/kg) markedly delayed or weakened KA-induced behavioral changes, such as increasing latency of WDS and generalized convulsion, shortening time of seizure and none of animal died during observed time. The concentration of NO 2-/NO 3- in the hippocampus increased immediately at 30 min and remained to 7 d after the administration of KA. Compared with control group (pretreatment with NS), the concentration of NO 2-/NO 3- in the hippocampus apparently increased at 3 h and 3 d after the administration of KA in the rats with L-Arg pretreatment. Conclusion: The endogenous NO (NO or NO derivatives) mediators may play an important role against excitotoxin induced seizures in rats.