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目的:对柴胡等7种中草药的超临界CO2萃取物进行抗惊厥作用的比较,并初步探讨其作用机制。方法:将昆明种小鼠1 060只随机分为11组,柴胡CO2萃取物组(柴Ⅰ)、柴胡CO2乙醇提取物组(柴Ⅱ)、石菖蒲CO2萃取物组(石Ⅰ)、石菖蒲CO2乙醇提取物组(石Ⅱ)、天南星CO2乙醇提取物组(天Ⅱ)、钩藤CO2乙醇提取物组(钩Ⅱ)、半夏CO2乙醇提取物组(半Ⅱ)、瑞香狼毒CO2萃取物组(狼Ⅰ)和柏子仁CO2萃取物组(柏Ⅰ)、托吡酯组、生理盐水组,每组分为4～6个剂量组,每个剂量组20只,ig给药,观察各剂量组对最大电休克(maximal electroshock seizure,MES)模型的对抗作用;以上述各药抗MES惊厥的ED50为给药剂量,观察ig各药对小鼠戊四唑惊厥模型(metrazol seizure test,MET)的对抗作用;由小鼠抗MES惊厥的ED95折算得到大鼠ig剂量,建立大鼠皮层定位注射青霉素点燃模型,比较各药对惊厥行为和脑电图的影响。结果:①9种受试中药提取物中天Ⅱ、钩Ⅱ、石Ⅰ、半Ⅱ、狼Ⅰ、柴Ⅰ、石Ⅱ对MES模型均有对抗作用,且量效均呈正相关性。②7种受试中药提取物均可延长MET惊厥潜伏期,数值由大到小排列依次为天Ⅱ、钩Ⅱ、石Ⅰ、半Ⅱ、狼Ⅰ、柴Ⅰ、石Ⅱ,其中天Ⅱ(11.06±4.32)min的作用效果优于托吡酯(9.57±4.47)min。③CO2萃取物较CO2乙醇萃取物起效快,作用持续时间短。(4)半Ⅱ、柴Ⅰ、天Ⅱ、钩Ⅱ、石Ⅰ、石Ⅱ均可不同程度的延长青霉素诱发的痫性发作潜伏期、减轻发作程度,延长痫性放电的潜伏期,减少痫波发放频率,减小放电最高波幅。结论:天Ⅱ、钩Ⅱ、石Ⅰ、半Ⅱ、狼Ⅰ、柴Ⅰ、石Ⅱ均可对抗小鼠MES和MET惊厥;半Ⅱ、柴Ⅰ、天Ⅱ、钩Ⅱ、石Ⅰ、石Ⅱ可抑制大鼠皮层定位注射青霉素诱发的癫痫发作和痫性放电,其中半Ⅱ是对抗青霉素点燃惊厥发作最有效的药物,且对该模型的对抗作用优于托吡酯。
OBJECTIVE: To compare the anticonvulsant effects of supercritical CO2 extracts of seven Chinese herbal medicines such as Bupleurum, and to explore its mechanism. Methods: A total of 1 060 Kunming mice were randomly divided into 11 groups: Bupleurum chinense CO2 extract group (Chai Ⅰ), Bupleurum chinense CO2 ethanol extract group (Chai Ⅱ) and Acorus calamus CO2 extract group (Shi Ⅰ) (Ⅱ), ethanol extract of Anemarrhenae CO2 (day Ⅱ), ethanol extract of Uncaria cannabina CO2 (hook Ⅱ), CO2 ethanol extract of Pinellia ternate (Ⅱ), Stellera chamaejasme The CO2 extract group (Wolf Ⅰ) and the Bozi seed CO2 extract group (Bo Ⅰ), the topiramate group and the saline group were divided into 4 to 6 dose groups, 20 in each dose group. Each dose group against maximal electroshock seizure (MES) model of antagonism; each of the above-mentioned anti-MES seizures ED50 for the dose, the observed ig each drug pentylene tetrazolium convulsions model (metrazol seizure test, MET) antagonistic effect; mouse anti-MES convulsive ED95 converted rat ig dose, the establishment of rat cortical injection of penicillin lit model to compare the seizure behavior and electroencephalogram EEG. Results: ①There were antagonistic effects of Tian Ⅱ, Hook Ⅱ, Shi Ⅰ, Ⅱ, Wolf Ⅰ, Chai Ⅰ and Shi Ⅱ on the MES model of nine kinds of Chinese herbal extracts, and the dose-effect showed a positive correlation. The 7 kinds of Chinese herbal extracts could prolong the latent period of MET convulsion, the order of the numbers was day Ⅱ, hook Ⅱ, stone Ⅰ, semi Ⅱ, wolf Ⅰ, wood Ⅰ, stone Ⅱ, and the days Ⅱ (11.06 ± 4.32 ) min is better than topiramate (9.57 ± 4.47) min. ③ CO2 extract CO2 CO2 extract faster onset, duration of action is shorter. (4) Semi-Ⅱ, ChaiⅠ, Ⅱ, HⅡ, ShiⅠ andⅡcan prolong the latent period of penicillin-induced seizure to a lesser degree, reduce the degree of seizure, prolong the latent period of epileptic discharge and reduce the frequency of epileptic seizure , Reduce the maximum discharge amplitude. Conclusion: Days Ⅱ, Ⅱ, Ⅰ, Ⅱ, Ⅲ, Ⅱ and Ⅱ can all antagonize MES and MET seizures in mice. Semi - Ⅱ, Chai Ⅰ, Ⅱ, H Ⅱ, Inhibition of penicillin-induced epileptic seizures and epileptic discharge induced by injection of penicillin in rat cortices, of which half Ⅱ is the most effective drug against penicillin-induced convulsions, and its antagonism against this model is superior to topiramate.