甘草甜素对癫痫持续状态大鼠神经保护作用及机制研究

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(P0.05);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(P0.05)。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。

Protective effects and mechanism of glycyrrhizin on status epilepticus rats

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 .