槐定碱的中枢兴奋作用及其对Glu、GABA表达的调节

Research on central pharmacological effects and Glu and GABA expression of sophoridine

目的探讨槐定碱的中枢药理作用及相关的作用机制。方法采用行为药理学方法观察槐定碱对正常小鼠一般行为、自主活动以及对戊巴比妥钠催眠作用的影响;对阈下剂量戊四氮、烟碱、士的宁、印防已毒素、异烟肼致惊厥的协同作用。采用单极引导法记录大鼠额叶皮层、海马的脑电图,并采用FFT技术定量分析槐定碱对脑电变化的影响。采用免疫组织化学技术(SABC法),观察槐定碱对大鼠额叶皮层、海马谷氨酸和γ-氨基丁酸免疫阳性神经细胞表达的影响。结果腹腔注射槐定碱5、10、20mg/kg,小鼠出现出汗、对峙、竖胡须、震颤等兴奋症状。10、20mg/kg能明显延长戊巴比妥钠致小鼠入睡潜伏期(P<0.01)。侧脑室注射槐定碱,0.1、0.2、0.4mg/只,大鼠额叶皮层、海马均出现痫样放电,痫样放电持续时间和频率均表现出明显的剂量依赖关系。与阈下剂量士的宁、印防己毒素、异烟肼有明显的致惊厥协同作用(P<0.01),但与戊四氮、烟碱无明显的协同作用(P>0.05)。侧脑室注射槐定碱0.2mg/只,明显增加大鼠大脑皮层、海马谷氨酸免疫阳性细胞数(P<0.01),γ-氨基丁酸阳性细胞数数目有所下降(P<0.01)。结论槐定碱对中枢神经系统具有明显的兴奋作用,其作用机制可能与谷氨酸和γ-氨基丁酸表达失衡有关。

Objective To study the central pharmacological effects and basic action mechanism of sophoridine.Methods Behavior method were employed to observe the effect of sophoridine on normal mice＇s autonomic activities and sleep latency,sleep-lasting time of mice under threshold dosage of pentobarbital,to observe the synergistic effects of sophoridine and pentylenetrazol,nicotin,stryncine,Isoniazid,picrotoxin at subthreshold dosage.Monopole leads was used in recording the EEG waves of frontal,amygdale,hippocampus,reticular formation.SABC was used to measure the effect of sophoridine on GLU and GABA immunoreaction＇s positive cells in CNS of rats.Results Sophoeidine administrated i.p.（10mg/kg,20mg/kg） suppressed autonomic activities of mice by the rate of 90%,80% and prolonged the sleeping latency of mice given pentobarbital （40mg/kg） advanced as well as shortened sleeping time （P0.01）.Intracerebroventricular injection （i.c.v.） （0.1mg/rat,0.2mg/rat,0.4mg/rat） showed epileptiform discharge electricity appeared in EEG of cerebral frontal,amygdale,hippocampus and reticular formation.Primary site might be in amygdale.The lasting time and frequency of epileptiform discharge electricity showed dosage-depending relationship.Administrating sophoridine i.c.v.（0.2mg/rat） significantly increase the number of Glu immunoreactions＇ positive cells （P0.01）,decrease the number of GABA immunoreactions＇ positive cells in rat＇s cerebral cortex and hippocampus （P0.01）.Conclusion This study suggests that sophoridine possessed the effect of excitation on CNS.Its mechanism may be associated with the expression imbalance of Glu and GABA.