芍药苷对幼鼠癫痫持续状态后海马神经元的保护作用  

Protective effect of paeoniflorin on hippocampal neurons and expression of DRP1 and ENT1 after status epilepticus in young rats

作　　者：郑婷婷 赵聪选 张莉[1] ZHENG Tingting;ZHAO Congxuan;ZHANG Li(Department of Neurology, Dalian Children's Hospital, Dalian 116000, Liaoning, China;Ultrasonic ECG Center, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China)

机构地区：[1]大连市儿童医院神经内科,辽宁大连116000 [2]辽宁中医药大学附属医院超声心电中心,辽宁沈阳110032

出　　处：《西部医学》2021年第6期839-845,共7页Medical Journal of West China

摘　　要：目的观察芍药苷对幼鼠癫痫持续状态(SE)后海马神经元的保护作用,探究其作用机制。方法3周龄SPF级Wistar大鼠72只,随机分为对照组、模型组、芍药苷组(50 mg/kg,i.p.),各组根据干预时间不同分别分为1、3、7 d三个亚组,每个亚组8只。除对照组外,其余各组幼鼠腹腔注射氯化锂-匹鲁卡品诱发SE,观察造模后幼鼠行为学变化,Nissl染色观察海马CA3区神经元变化,ELISA法检测海马组织超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量,Western Blot和qRT-PCR法检测B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、线粒体动力学相关蛋白(DRP1)和平衡型核苷转运载体-1(ENT1)蛋白和mRNA表达情况。结果与对照组比较,模型组大鼠海马CA3区神经元受损明显,在第7天时受损最显著,海马组织中SOD活力降低,MDA含量增加,Bax、DRP1和ENT1蛋白和mRNA表达增加,Bcl-2蛋白和mRNA表达减少。与模型组比较,芍药苷组大鼠海马CA3区受损程度减轻,海马组织SOD活力增加,MDA含量减少,Bax、DRP1和ENT1蛋白和mRNA表达减少,Bcl-2蛋白和mRNA表达增加。上述指标差异均有统计学意义(P<0.05)。结论芍药苷对幼鼠癫痫持续状态后海马神经元损伤具有保护作用,其作用机制可能与抑制DRP1和ENT1的活化有关。Objective To observe the protective effect of paeoniflorin on hippocampal neurons after status epilepticus(SE)in young rats and explore its mechanism.Methods 723-week-old SPF Wistar rats were randomly divided into control group,model group and paeoniflorin group(50 mg/kg,i.p.).Each group was divided into three subgroups of 1 d,3 d,and 7 d according to the intervention time,with 8 rats in each subgroup.Except for the control group,SE was induced by intraperitoneal injection of lithium pilocarpine in the rest groups.Observe the behavioral changes of young rats after modeling.Nissl staining was used to observe neuronal changes in hippocampal CA3 area.ELISA was used to detect superoxide dismutase(SOD)activity,malondialdehyde(MDA)content in hippocampus.Western Blot and qRT-PCR methods to detect B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein gene(Bax),mitochondrial dynamics related protein(dynamin-related protein 1,DRP1)and balanced nucleoside transporter-1(ENT1)protein and mRNA expression.Results Compared with the control group,the neurons in the CA3 area of the hippocampus in the model group were significantly damaged,and the damage was most significant on day 7.In hippocampus,SOD activity decreased,MDA content increased,Bax,DRP1 and ENT1 protein and mRNA expression increased,and Bcl-2 protein and mRNA expression decreased.Compared with the model group,the damage to hippocampal CA3 area of rats in the paeoniflorin group was reduced,SOD activity in hippocampus increased,MDA content decreased,Bax,DRP1 and ENT1 protein and mRNA expression decreased,and Bcl-2 protein and mRNA expression increased.The differences in the above indicators were statistically significant(P<0.05).Conclusion Paeoniflorin has a protective effect on hippocampal neuron damage after status epilepticus in young rats,and its mechanism may be related to inhibiting the activation of DRP1 and ENT1.

关 键 词：癫痫持续状态 芍药苷 海马 神经元 DRP1 ENT1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]