目的 探讨北柴胡Bupleurum chinense地上部分多糖组分(polysaccharides from aerial parts of B. chinense，ABP)对戊四唑致痫小鼠的预防作用及作用机制。方法 C57BL/6小鼠随机分为对照组、模型组、丙戊酸钠(125 mg/kg)组、癫痫宁片(1200 mg/kg)组和ABP高、低剂量(100、25 mg/kg)组，每组10只。各给药组ig相应药物，对照组和模型组ig等体积0.5%羧甲基纤维素钠溶液，1次/d，连续7 d。末次给药后60 min，除对照组外，其余各组ip戊四唑(60 mg/kg)。通过行为学评价ABP预防癫痫的作用；采用苏木素-伊红(HE)染色、免疫组化法检测海马神经元病理形态学变化；采用ELISA法测定海马组织中半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3，Caspase-3)、胶质纤维酸性蛋白(glial fibrillary acidic protein，GFAP)、谷氨酸脱羧酶65(glutamic acid decarboxylase 65，GAD65)、GAD67、G蛋白偶联的内向整流钾通道1(G protein gated inwardly rectifying K channels 1，GIRK1)、N-甲基-D-天冬氨酸受体1(N-methyl-D-aspartic acid receptor，NMDAR1)、γ-氨基丁酸A型受体(γ-aminobutyric acid type A，GABA AR)水平；采用Western blotting检测海马组织中DJ-1、特异性蛋白1(specificity protein 1，SP1)、p-SP1、核因子E2相关因子2(nuclear factor erythroid 2-related factor 2，Nrf2)、血红素加氧酶-1(heme oxygenase-1，HO-1)蛋白表达。采用过氧化氢(hydrogen peroxide，H₂O₂)诱导的PC12细胞氧化应激模型进行验证。结果 与模型组比较，ABP明显改善小鼠癫痫症状，表现为躯体僵直率和死亡率降低等(P＜0.01)；海马锥体细胞排列规则，结构清晰，GFAP阳性表达面积明显降低；显著降低海马组织中Caspase-3、GFAP、GAD65、GAD67、GIRK1及NMDAR1水平(P＜0.01)，升高GABA AR水平(P＜0.01)；显著下调癫痫小鼠海马组织和H₂O₂诱导的PC12细胞中DJ-1、p-SP1、Nrf2及HO-1蛋白表达(P＜0.01)。结论 ABP可以减轻癫痫发作期间DJ-1/Nrf2/HO-1介导的癫痫氧化应激，从而发挥预防癫痫的作用。

Objective To investigate the preventive effect and mechanism of polysaccharide from aerial parts of Bupleurum chinense (ABP) on pentylenetetrazole-induced epilepsy in mice. Methods C57BL/6 mice were randomly divided into control group, model group, sodium valproate (125 mg/kg) group, epileptic tablets (1200 mg/kg) group and ABP high-, low-dose (100, 25 mg/kg) groups, with 10 mice in each group. Each administration group was ig corresponding drug, control group and model group were ig equal volume 0.5% sodium carboxymethyl cellulose solution, once a day for 7 d. 60 min after the last administration, except for control group, other groups were ip pentylenetetrazole (60 mg/kg). The effect of ABP on preventing epilepsy was evaluated by behavior; The pathomorphological changes of hippocampal neurons were detected by hematoxylin eosin (HE) staining and immunohistochemistry; The levels of cystein-asparate protease-3 (Caspase-3), glial fibrillary acidic protein (GFAP), glutamic acid decarboxylase 65 (GAD65), GAD67, G protein gated inwardly rectifying K channels 1 (GIRK1), N-methyl-D-aspartate acid receptor 1 (NMDAR1) and γ-aminobutyric acid type A receptor (GABA AR) in hippocampus were detected by ELISA; Western blotting was used to detect DJ-1, specific protein 1 (SP1), p-SP1, nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression in hippocampus. The oxidative stress model of PC12 cells induced by hydrogen peroxide (H₂O₂) was used to verified. Results Compared with model group, ABP significantly improved the epileptic symptoms of mice, which showed a decrease in rate of body stiffness and mortality (P < 0.01); Hippocampal pyramidal cells were regularly arranged with clear structure, and GFAP positive expression area was reduced; The levels of Caspase-3, GFAP, GAD65, GAD67, GIRK1 and NMDAR1 in hippocampus were significantly decreased (P < 0.01); DJ-1, p-SP1, Nrf2 and HO-1 protein expressions in hippocampus of epileptic mice and H₂O₂-induced PC12 cells were significantly decreased (P < 0.01). Conclusion ABP can reduce DJ-1/Nrf2/HO-1 mediated oxidative stress during epileptic seizures, thus playing a role in preventing epilepsy.

国家自然科学基金面上项目(81973440)；黑龙江省“头雁”团队支持项目(黑龙江省头雁行动领导小组文件[2019]5号)