甘草甜素对癫痫持续状态大鼠神经保护作用及机制研究

摘要

Objective To study the protective effects and mechanism of glycyrrhizin on neuronal damage of Status Epilepticus(SE)rathippocampus.Methods 60 healthy adult male Sprague-Dawley rats were included in thisstudy.SE rat model were induced by intraperitoneally injected with lithium and pilocarpine method .All rats were randomly divided in-to three groups:(SE+GL)-treated group,(SE+S) group and normal control group.According to different GL dosage,(SE+GL)-treated group were divided into three subgroup:high glycyrrhizin group ( HGL, 20 mg/kg ) , middle glycyrrhizin group (MGL,10 mg/kg),low glycyrrhizin group (LGL,5 mg/kg).The hippocampal neuronal damage was detected by nissl's staining,levels of HMGB1 in serum and hippocampus were determined with enzyme linked immunosorbent assay ( ELISA) and western blot .Results Compared with those in ( SE+S) group,the cortical neurons damage significantly re-duced and HMGB1 expressions were significantly decreased in (SE+GL)-treated group (P<0.05).Conclusion GL sig-nificantly decreased neuronal damage in the cortex of SE rat models ,and it turned out dose-dependent .These results suggest that GL affords neuroprotective effects in lithium-pilocarpine induced SE rats ,which may via inhibiting the expressions of HMGB1 in serum and cortical neurons .%目的 研究甘草甜素(glycyrrhizin,GL)对癫痫持续状态大鼠(status epilepticus,SE)神经损伤保护作用及相关分子机制.方法 取清洁健康成年雄性SD大鼠60只,采用腹腔注射氯化锂-匹罗卡品的方法建立大鼠癫痫持续状态(SE)模型,随机分为甘草甜素组(SE+GL)和生理盐水组(SE+S),分别经尾静脉给予甘草甜素及生理盐水进行干预,取正常大鼠作为对照组(control group,C);根据给予GL剂量不同将其分为高剂量组(HGL,20 mg/kg)、中剂量组(MGL,10 mg/kg)及低剂量组(LGL,5 mg/kg);通过尼氏染色(NS)观察各组大鼠SE后24 h时大脑皮质神经元损伤情况,分别采用酶联免疫吸附法(ELISA)和蛋白印迹实验(Western blot)检测各组大鼠SE后24 h时血清及大脑皮质中高迁移率族蛋白(HMGB1)的表达水平.结果 SE+S组大鼠大脑皮质神经元在癫痫持续状态后24 h明显受损,SE+GL各组皮质受损神经元数量较SE+S组减少,且在不同给药剂量组间存在显著差异(P<0.05);SE+GL各组在SE后24 h时大脑皮质及血清中HMGB1的表达水平较SE+S组显著降低,差异具有统计学意义(P<0.05).结论 经尾静脉给予GL能有效地减少SE后大鼠大脑皮质神经元损伤,且其神经保护作用呈剂量依赖性,其机制可能与其抑制血清及大脑皮质炎性因子HMGB1的表达有关.