摘要
目的探讨银杏内酯B(GB)对癫痫模型大鼠学习记忆能力和海马神经元病变的影响。方法将180只雄性SD大鼠按随机数字表法分为空白对照组、模型组、GB低、中、高剂量组(2.5、5、10 mg/kg)和丙戊酸钠(VPA)组(300 mg/kg),每组30只。除空白对照组外,其余各组采用氯化锂-匹罗卡品诱导制备癫痫大鼠模型;注射匹罗卡品前30 min,GB低、中、高剂量组分别腹腔注射浓度为0.5、1、2 mg/ml的GB溶液5 ml/kg;VPA组腹腔注射浓度为60 mg/ml的VPA溶液5 ml/kg;模型组和空白对照组腹腔注射0.9%氯化钠注射液5 ml/kg。记录各组大鼠癫痫发作潜伏期、发作持续时间并采用Racine评分评估癫痫发作程度;Morris水迷宫实验测定大鼠学习记忆能力;HE染色进行海马神经元病理学检查;黄嘌呤氧化法和钼酸铵法分别检测超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力、硫代巴比妥酸法检测丙二醛(MDA)水平;ELISA检测海马组织TNF-α、IL-1β、IL-6水平。结果与模型组比较,GB中、高剂量组和VPA组大鼠癫痫发作潜伏期延长、发作持续时间缩短、发作程度降低(均P<0.01);逃避潜伏期缩短且穿越平台次数增多(P<0.05或0.01);海马神经元病变明显改善;海马组织SOD、CAT活性升高且MDA水平降低(P<0.05或0.01);TNF-α、IL-1β、IL-6水平降低(均P<0.01)。与VPA组比较,GB高剂量组大鼠癫痫发作潜伏期延长,发作持续时间缩短,发作程度降低,逃避潜伏期缩短且穿越平台次数增多,SOD活性升高且MDA水平降低,TNF-α、IL-6水平降低(P<0.05或0.01)。结论GB能够延长癫痫模型大鼠癫痫发作潜伏期,缩短发作持续时间、降低发作强度,改善癫痫大鼠学习记忆能力,其机制可能与GB通过抑制氧化应激和炎症反应而保护海马神经元有关。
Objective To investigate the effects of ginkgolide B(GB)on the learning and memory ability and its mechanism in epilepsy rats.Methods One hundred eighty male SD rats were randomly divided into blank control group(normal saline),model group(normal saline),low,medium and high dose GB groups(2.5,5,10 mg/kg)and sodium valproate(VPA)group(300 mg/kg)with 30 rats in each group.The epilepsy rat model was induced by intraperitoneal injection of lithium chloride and pilocarpine,30 min before pilocarpine injection,the corresponding drugs were given to rats in each group by administered intraperitoneal.The incubation period and duration of seizures were recorded,and the degree of seizures was evaluated by Racine score,the learning and memory ability was measured by Morris water maze experiment.The pathological examination of hippocampus was performed with HE staining.The activity of superoxide dismutase(SOD),catalase(CAT)were detected by xanthine oxidation method and ammonium molybdate method,and the malondialdehyde(MDA)content was detected by thiobarbituric acid method,the level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)were detected by ELISA method.Results Compared with model group,the incubation period of seizures in medium,high-dose GB groups and VPA group was prolonged,the duration of seizures was shortened,and the degree of seizures was reduced(P<0.05 or 0.01),the escape latency was shortened and the number of crossing platforms was increased(all P<0.01),the lesions of hippocampal neuron were attenuated,the activity of SOD and CAT was increased and MDA content decreased(P<0.05 or 0.01),the TNF-α,IL-1β,IL-6 levels were decreased(all P<0.01).Compared with VPA group,the incubation period was prolonged in rats of high-dose GB group,the seizure duration was shortened and the seizures was reduced(P<0.05),the escape latency was shortened and the number of crossing platforms was increased,the activity of SOD was increased and MDA content decreased,the TNF-α,IL-6 levels were decreased(P<0.05 or 0.01).Conclusion GB can prolong the incubation period of epilepsy attack,shorten the duration of the attack,reduce the intensity of the attack,and improve the learning and memory ability in epilepsy rats,which may be related to the protection of hippocampal neurons by inhibiting oxidative stress and in-flammation.
作者
鲁光辉
李新峰
冯亮
罗玲
王海华
LU Guanghui;LI Xinfeng;FENG Liang;LUO Ling;WANG Haihua(Department of Neurology,Handan Second Hospital,Handan 056000,China)
出处
《浙江医学》
CAS
2021年第19期2058-2062,I0003,共6页
Zhejiang Medical Journal
基金
河北省医学科学研究课题计划(20191789)。
关键词
银杏内酯B
癫痫
学习记忆
行为学
海马
Ginkgolide B
Epilepsy
Learning and memory
Oxidative stress
Inflammation
