甘草甜素对癫痫持续状态大鼠神经保护作用及机制研究  

Protective effects and mechanism of glycyrrhizin on status epilepticus rats

作　　者：王林 李亚军[2] 张蓓[2] 常明则[3] 石少亭 张世俊[2] 折潇[2] 杨春梅[1] 

机构地区：[1]宁夏医科大学临床医学院,宁夏银川750003 [2]西安医学院第一附属医院神经内科,陕西西安710077 [3]西安市中心医院神经内科,陕西西安710021

出　　处：《中风与神经疾病杂志》2017年第10期897-901,共5页Journal of Apoplexy and Nervous Diseases

基　　金：陕西省科技统筹创新工程计划(No.S2015TLSF0010);陕西省教育厅基金(No.11JK0715);陕西省卫生厅科研基金(No.2012D43)

摘　　要：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。Objective To study the protective effects and mechanism of glycyrrhizin on neuronal damage of Status Epilepticus（SE） rat hippocampus.Methods 60 healthy adult male Sprague-Dawley rats were included in this study.SE rat model were induced by intraperitoneally injected with lithium and pilocarpine method.All rats were randomly divided into 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 reduced and HMGB1 expressions were significantly decreased in（SE ＋ GL）-treated group（P〈0.05）.Conclusion GL significantly 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.

关 键 词：癫痫持续状态 甘草甜素 大脑皮质神经元 HMGB1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]