槐定碱致痫大鼠模型的建立及血清TNF-α和IL-1β含量变化的研究

Establishment of an epilepsy model induced by SRI in rats and study on serum level of TNF-α and IL-1β

目的建立槐定碱(Sophoridien,SRI)诱导大鼠癫痫模型,同步观察槐定碱致痫大鼠行为和脑电的变化,探讨细胞因子与癫痫发病之间的关系。方法采用序贯法测定SRI大鼠腹腔注射的半数致死量(LD50)。将SD大鼠随机分为生理盐水对照组和实验组,实验组又分为6个剂量组,依照寇氏法安排SRI剂量。腹腔注射SRI后,观察大鼠行为变化并描记大鼠海马脑电图,用改进寇氏法测定SRI致癫痫的半数有效量(ED50);同时运用放射免疫法,检测大鼠血清TNF-α、IL-1β的水平。结果SRI腹腔注射的LD50值为46.66mg/kg;腹腔注射SRI后,大鼠出现痫性行为发作,海马EEG表现为典型的痫样脑电变化;SRI腹腔注射致癫痫的ED50为40.66mg/kg;实验组大鼠血清中TNF-α、IL-1β含量均明显高于对照组(P<0.01)。结论槐定碱腹腔注射可在大鼠引发典型的痫样发作行为和痫样脑电;TNF-α、IL-1β在槐定碱所致的癫痫发病中起促进作用,是癫痫发病的基础之一。

Objective To establish Sophoridien （SRI） induced epileptic rats model, investigate the changes of behavior and EEG on epilepsy rats caused by SRI in - synchronism, and approach the relationships between cytokine and the mechanism for pathogenesis of epilepsy. Methods Sequential analysis was used to determine the median lethal dose （ LD50 ） in rats; SD rats were divided randomly into NS control group and six different experimental groups, and the doses of SRI for estimating kindling epilepsy were scheduled according Karber＇s method. SRI was intraperitoneally injected in rats and to observe the changes of rat＇s behavior and EEG record. The median effective dose （ED50） in rats with epilepsy was determined using refining Karber＇s method. At the same time, the serum levels TNF - α and IL - 1β of each group was measured by means of radioimmunoassay （RIA）. Results The LD50 in rats for SRI were 46. 66 mg/kg. The kindling model of rats was induced by SRI intraperitoneal injection. The behavioral seizure was observed, EEG showed a representative epileptic pattern. The ED50 in rats with epilepsy for SRI were 40.66mg/kg. The serum levels TNF - α and IL - 1β were significantly higher in model group than those in control group （P 〈 0. 01 ）. Conclusion SRI can induce typical behavioral seizure and electrographic seizure of rats; TNF - α and IL - 1β may play a promoting role in SRI - induced epilepsy and they may be the base of pathogenesis of epilepsy.