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桑椹花青素-3-葡萄糖苷对癫痫模型小鼠的保护作用及海马

BDNF/TrkB通路的影响 Δ

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王 芳 ，侯自立 ，韩 冰 ，解国圣 ，张艳玲 （1.邢台市人民医院儿三科，河北 邢台 054000；2.邢台市人民医
院药剂科，河北 邢台 054000）
中图分类号 R285 文献标志码 A 文章编号 1001-0408（2020）03-0335-05
DOI 10.6039/j.issn.1001-0408.2020.03.16

摘 要 目的：研究桑椹花青素-3-葡萄糖苷对癫痫模型小鼠的保护作用及海马脑源性神经营养因子（BDNF）/酪氨酸激酶受体B
（TrkB）通路的影响。方法：将120只C57BL/6小鼠随机分为正常组、模型组、单药（桑椹花青素-3-葡萄糖苷）和激动剂联用组（桑椹
花青素-3-葡萄糖苷+TrkB激动剂LM22B-10），每组30只。单药组和激动剂联用组小鼠每天灌胃600 μg/kg桑椹花青素-3-葡萄糖
苷1次、连续给药6周，激动剂联用组小鼠在给药第6周时每天侧脑室注入LM22B-10（5 mg/kg）1次；正常组和模型组小鼠灌胃等
体积生理盐水。末次给药后，除正常组外，其余各组小鼠均采用氯化锂-匹罗卡品建立癫痫模型。造模成功后，各组分别取10只小
鼠记录其癫痫自发性再发作的潜伏期、发作频率及持续时间，每天观察6 h，连续观察4周；并于造模第14、28、36天记录其脑电图，
统计1 h内脑电波异常发生次数。于造模后第6天，各组分别取10只小鼠检测其血清钙离子水平，并取各组剩余10只小鼠检测其
海马组织中BDNF mRNA及蛋白表达。结果：与正常组比较，模型组小鼠癫痫自发性再发作的潜伏期、发作频率、持续时间及造模
第 14、28、36 天脑电波异常发生次数均显著增加（P＜0.05），血清钙离子水平及海马 BDNF mRNA、蛋白相对表达量均显著升高
（P＜0.05）。与模型组比较，单药组小鼠癫痫自发性再发作行为的潜伏期、发作频率、持续时间及造模第28、36天脑电波异常发生
次数均显著减少（P＜0.05），血清钙离子水平及海马BDNF mRNA、蛋白相对表达量均显著降低（P＜0.05）；与单药组比较，激动剂
联用组小鼠癫痫自发性再发作的潜伏期、发作频率、持续时间及造模第28、36天脑电波异常发生次数均显著增加（P＜0.05），血清
钙离子水平及海马BDNF mRNA、蛋白相对表达量均显著升高（P＜0.05）。结论：桑椹花青素-3-葡萄糖苷对癫痫模型小鼠具有一
定的保护作用，其机制可能与抑制海马BDNF/TrkB通路的激活有关。
关键词 桑椹花青素-3-葡萄糖苷；癫痫；脑源性神经营养因子；酪氨酸激酶受体B；机制；小鼠

Study on Protection Effect of Mulberry Anthocyanin-3-glucoside on Epilepsy Model Mice and the Effect of
Hippocampal BDNF/TrkB Pathway
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WANG Fang ，HOU Zili ，HAN Bing ，XIE Guosheng ，ZHANG Yanling（1.Dept. Three of Pediatrics，Xingtai
People’s Hospital，Hebei Xingtai 054000，China；2.Dept. of Pharmacy，Xingtai People’s Hospital，Hebei
Xingtai 054000，China）
ABSTRACT OBJECTIVE：To study the protection effects of mulberry anthocyanin-3-glucoside on epilepsy model mice and the
effect of hippocampal brain derived neurotrophic factor （BDNF）/tyrosine kinase B （TrkB） pathway. METHODS：Totally 120
C57BL/6 mice were randomly divided into normal group，model group，single medication group （mulberry anthocyanin-3-
glucoside），agonist combination group（mulberry anthocyanin-3-glucoside+TrkB agonist LM22B-10），with 30 mice in each group.
single medication group and agonist combination group were given mulberry anthocyanin-3-glucoside 600 μ g/kg intragastrically
once a day，for consecutive 6 weeks. The agonist combination group was given LM22B-10（5 mg/kg）via the lateral ventricle once
a day at 6th week. Normal group and model group were given constant volume of normal saline intragastrically. After last
medication，except for normal group，other groups were given lithium chloride-pilocarpine to establish epilepsy model. After
modeling，10 mice in each group were taken to record the latency，frequency and duration of spontaneous recurrent epilepsy，
observed for 6 hours a day for 4 weeks；EEG was recorded on the 14th，28th and 36th day after modeling，and the abnormal
frequency of EEG in 1 h was counted. On the 6th day of modeling，other 10 mice in each group were taken to detect the serum
calcium level，and the remaining 10 mice in each group were taken to detect the expressions of BDNF mRNA and protein in the
hippocampus. RESULTS：Compared with normal group，latency，frequency and duration of spontaneous recurrent epilepsy and the
times of abnormal brain wave on the 14th，28th and 36th day after modeling were increased significantly in model group（P＜
0.05）. The serum calcium level， mRNA and protein
Δ 基金项目：2019年度河北省医学科学研究课题（No.20191712）
expression of BDNF in hippocampus were increased
＊主治医师，硕士。研究方向：神经系统和内分泌系统疾病。
E-mail：wangfang7699@126.com significantly （P＜0.05）. Compared with model group， the
# 通信作者：主任医师，硕士。研究方向：儿科神经系统和内分泌 latency，frequency，duration of spontaneous recurrent epilepsy
系统疾病。E-mail：63725878@qq.com and the times of abnormal brain wave on the 28th and 36th

中国药房 2020年第31卷第3期 China Pharmacy 2020 Vol. 31 No. 3 ·335 ·