【作者】 何欣嘏；

【导师】 王明正；

【作者基本信息】 山西医科大学 ， 药理学， 2006， 硕士

【摘要】 目的比较五种单味中药醇提物(全蝎SP、僵蚕SS、地龙LB、蝉衣CS、蜈蚣CP)的抗惊厥作用,并探讨其作用机制。方法①采用最大电休克惊厥模型,分析灌胃(ig)小鼠各药的量效和时效关系,比较其效价强度和效能;②采用戊四唑惊厥模型,比较ig小鼠各药的惊厥潜伏期、抗惊厥率和死亡率;③采用药效法,运用数学模式及参数来模拟各药在体内的药效动力学过程;④制备大鼠皮层定位注射青霉素点燃模型,采用RM6240C型多道生理信号采集处理系统记录脑电图,比较ig各药对痫性发作潜伏期及发作程度、痫性放电潜伏期、痫波发放频率及最高波幅的影响;⑤采用HPLC法测定海马区癫痫相关递质的含量,比较各药对Glu、Asp、Gly、GABA的影响。结果及结论(1)五种受试中药醇提物对MES模型均有对抗作用,量效均呈正相关性,效能从大到小依次为:全蝎、僵蚕、地龙、蝉衣、蜈蚣;效价强度由大到小依次为:全蝎、蝉衣、僵蚕、蜈蚣、地龙。(2)五种受试中药醇提物中除蜈蚣外,其余四种提取物均可对抗MET发作,按各药的ED95给药,MET惊厥潜伏期延长数值从大到小排列依次为:僵蚕、全蝎、蝉蜕、地龙,其中僵蚕的作用优于拉莫三嗪(LTG)。(3)五种受试中药醇提物均在给药后30min起效,平均1h左右达峰,蜈蚣组作用持续时间最短仅达2h,全蝎组作用持续时间最长,达7h。从体存药效动力学研究所得结果可以推测出,五种提取物均属于短半效期制剂。(4)全蝎是对抗青霉素点燃惊厥发作最有效的药物,而且对该模型的对抗作用与拉莫三嗪相当;僵蚕、蝉蜕和地龙对该模型也有较好的对抗作用,而蜈蚣则无效。(5)全蝎和地龙的抗惊厥作用机制主要是通过显著增加大鼠海马GABA的含量、提高GABA能神经功能而实现的;蝉蜕通过降低Glu的含量,限制Glu兴奋系统功能而发挥抗惊厥作用;僵蚕即可以增加GABA的含量,又能降低Glu的含量,其抗惊厥作用可能与增强GABA能神经抑制功能和/或抑制Glu兴奋功能有关。而蜈蚣对大鼠海马区Glu、GABA等癫痫相关递质的含量变化没有显著影响。更多还原

【Abstract】 Objective To compare the pharmacodynamics of five alcoholic extractives(Scorpion,SP、Centipede,CP、Stiff Silkorm,SS、Lumbricus,LB、Cicada Slough,CS)on anticonvulsion,and explore their mechanism of anticonvulsant action. MethodsⅠMaximal electroshock seizure(MES) was adopted to analyse the relative of dose and effect, relative of time and effect, including maximal efficacy and potency of these five extractives in mice given by ig administration.ⅡMetrazol seizure test(MET) was used to compare seizure latency, anticonvulsant rate and mortality of mice with every extractives.ⅢPharmacodynamic parameters of five alcoholic extractives were assayed by means of Pharmacological Effective Method.ⅣUsing the model of seizure rats induced by penicillin localized injected in cortex,we studied the effect of extractives on seizure latency, frequency of epileptiform discharge, highest wave of hippocampus EEG(Recoded by RM6240C multichannel physiological signal collection and analysis recorde), the changes of convulsant behaviors and the latency of seizure.ⅤThe neurotransmitters content related to epilepsy in brain were determined by high performance liquid chromatography(HPLC) in order to compare the effect of extractives on Glu, Asp, Gly and GABA of hippocampus. Results and conclusionsⅠall the five extractions could dose-dependently antagonize MES in mice. Maximum efficacy of extractions ranged from maximum to minimum were SP, SS, LB, CS, CP, and the sequence of potency were SP, CS, SS, CP, LB.ⅡExcept for CP, all the other four extractions could prolong latent period on MET in mice, and the sequence from maximum to minimum were SS, SP, CS, LB, CP, at the same time, The effect of SS was better than that of LTG.ⅢThe effect of these extractions produced after 30min ig, and peaked after about 1h on average, however, persistent time of them was different. Persistent time of CP was 2h, but that of SP lasted for about 7h. It could be conjectured that all of the five alcoholic extractives belong to short-half period preparations studied by Pharmacological Effect Method.ⅣSP was the most effective extraction to antagonize the penicillin-induced seizure. Anticonvulsant properties of SP resembled LTG, SS, CS, LB also had effect in penicillin-kindling model, but CP hadn’t.ⅤThe anticonvulsant mechanism of SP and LB was probably due to increasing the level of GABA, however, CS was related to decreasing Glu level. The anticonvulsant mechanism of SS might have relationship with the two mentioned aspects. While CP had no obvious effect on neurotransmitters content related to更多还原