【摘要】：目的觀察鹽酸小檗堿(BBH)預(yù)處理對青霉素鈉誘發(fā)小鼠癲癇發(fā)作程度、發(fā)作潛伏期的影響,并探討其機(jī)制。方法雄性昆明種小鼠50只,適應(yīng)性飼養(yǎng)3 d后隨機(jī)分為生理鹽水組、模型組、丙戊酸鈉(VPA)組、BBH1組、BBH2組。VPA組腹腔注射VPA 40 mg/kg,BBH1組以BBH 25 mg/kg灌胃,BBH2組以BBH 50 mg/kg灌胃,生理鹽水組和模型組分別以等量生理鹽水和β-環(huán)糊精灌胃。各組每天給藥1次,連續(xù)給藥3 d。至末次給藥次日,除生理鹽水組外,其余四組均腹腔注射青霉素鈉700萬IU/kg誘發(fā)癲癇。記錄各組小鼠從給藥到出現(xiàn)癲癇癥狀的潛伏期。根據(jù)Racine分級標(biāo)準(zhǔn)評估癲癇發(fā)作分級,記錄癲癇大發(fā)作(Ⅲ級)發(fā)生情況。發(fā)作持續(xù)1 h后,頸椎脫臼處死動物并斷頭取腦,采用液相色譜-質(zhì)譜聯(lián)用法(LC-MS)檢測海馬組織中的谷氨酸(Glu)、γ-氨基丁酸(GABA)、五羥色胺(5-HT)。結(jié)果模型組癲癇發(fā)作Ⅲ級2只、Ⅳ級7只、Ⅴ級1只,癲癇大發(fā)作8只;VPA組Ⅲ級6只、Ⅳ級3只、Ⅴ級1只,共4只達(dá)到大發(fā)作;BBH1組Ⅲ級3只、Ⅳ級6只、Ⅴ級1只,7只大發(fā)作;BBH2組Ⅱ級1只、Ⅲ級6只、Ⅳ級3只、Ⅴ級1只,癲癇大發(fā)作4只。BBH2組小鼠癲癇發(fā)作達(dá)到Ⅲ級以上的數(shù)量與模型組相比,P均0.05。模型組、VPA組、BBH1組、BBH2組癲癇發(fā)作潛伏期分別為(142.4±68.4)、(237.5±132.6)、(246.9±59.8)、(260.5±52.4)s,BBH1組、BBH2組癲癇發(fā)作潛伏期較模型組延長(P均0.05)。VPA組海馬組織中GABA表達(dá)水平高于模型組(P0.05)。模型組Glu/GABA高于生理鹽水組(P0.05);VPA組Glu/GABA低于模型組(P0.05);BBH1組、BBH2組Glu/GABA低于模型組,但差異無統(tǒng)計學(xué)意義。BB1組Glu/5-HT低于模型組(P0.05)。結(jié)論 BBH預(yù)處理有助于降低小鼠癲癇發(fā)作分級,延長癲癇發(fā)作潛伏期,其中50 mg/kg劑量效果優(yōu)于25mg/kg劑量;BBH的抗癲癇機(jī)制可能與調(diào)節(jié)海馬組織內(nèi)神經(jīng)遞質(zhì)水平有關(guān)。
[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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