盐酸小檗碱预处理对青霉素钠诱发小鼠癫痫发作程度、发作潜伏期的影响及其机制

发布时间：2018-10-05 21:31

【摘要】：目的观察盐酸小檗碱(BBH)预处理对青霉素钠诱发小鼠癫痫发作程度、发作潜伏期的影响,并探讨其机制。方法雄性昆明种小鼠50只,适应性饲养3 d后随机分为生理盐水组、模型组、丙戊酸钠(VPA)组、BBH1组、BBH2组。VPA组腹腔注射VPA 40 mg/kg,BBH1组以BBH 25 mg/kg灌胃,BBH2组以BBH 50 mg/kg灌胃,生理盐水组和模型组分别以等量生理盐水和β-环糊精灌胃。各组每天给药1次,连续给药3 d。至末次给药次日,除生理盐水组外,其余四组均腹腔注射青霉素钠700万IU/kg诱发癫痫。记录各组小鼠从给药到出现癫痫症状的潜伏期。根据Racine分级标准评估癫痫发作分级,记录癫痫大发作(Ⅲ级)发生情况。发作持续1 h后,颈椎脱臼处死动物并断头取脑,采用液相色谱-质谱联用法(LC-MS)检测海马组织中的谷氨酸(Glu)、γ-氨基丁酸(GABA)、五羟色胺(5-HT)。结果模型组癫痫发作Ⅲ级2只、Ⅳ级7只、Ⅴ级1只,癫痫大发作8只;VPA组Ⅲ级6只、Ⅳ级3只、Ⅴ级1只,共4只达到大发作;BBH1组Ⅲ级3只、Ⅳ级6只、Ⅴ级1只,7只大发作;BBH2组Ⅱ级1只、Ⅲ级6只、Ⅳ级3只、Ⅴ级1只,癫痫大发作4只。BBH2组小鼠癫痫发作达到Ⅲ级以上的数量与模型组相比,P均0.05。模型组、VPA组、BBH1组、BBH2组癫痫发作潜伏期分别为(142.4±68.4)、(237.5±132.6)、(246.9±59.8)、(260.5±52.4)s,BBH1组、BBH2组癫痫发作潜伏期较模型组延长(P均0.05)。VPA组海马组织中GABA表达水平高于模型组(P0.05)。模型组Glu/GABA高于生理盐水组(P0.05);VPA组Glu/GABA低于模型组(P0.05);BBH1组、BBH2组Glu/GABA低于模型组,但差异无统计学意义。BB1组Glu/5-HT低于模型组(P0.05)。结论 BBH预处理有助于降低小鼠癫痫发作分级,延长癫痫发作潜伏期,其中50 mg/kg剂量效果优于25mg/kg剂量;BBH的抗癫痫机制可能与调节海马组织内神经递质水平有关。
[Abstract]:Objective to observe the effects of berberine hydrochloride (BBH) pretreatment on the seizure severity and seizure latency in mice induced by penicillin sodium, and to explore its mechanism. Methods Fifty male Kunming mice were randomly divided into normal saline group and sodium valproate (VPA) group. VPA 40 mg/kg,BBH1 group was injected intraperitoneally with BBH 25 mg/kg and treated with BBH 50 mg/kg. The saline group and the model group were perfused with the same amount of saline and 尾-cyclodextrin respectively. Each group was given drug once a day for 3 days. To the next day after the last administration, the other four groups were all intraperitoneally injected penicillin sodium 7 million IU/kg to induce epilepsy except the saline group. The incubation period from administration to epileptic symptoms in each group was recorded. According to the Racine classification criteria, the epileptic seizure grade was evaluated, and the occurrence of the epileptic seizure (grade 鈪，

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