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电针通过提高血脑屏障通透性增强抗癫痫药对急性癫痫发作模型的作用研究

笪晓丽 徐层林 张小杰 赵新月 龚祎位 仇肖允 李立红 王瑞明 汪仪 陈忠

临床传统医学和药理学(英文)2025,Vol.6Issue(4):57-66,10.
临床传统医学和药理学(英文)2025,Vol.6Issue(4):57-66,10.DOI:10.1016/j.ctmp.2025.200247

电针通过提高血脑屏障通透性增强抗癫痫药对急性癫痫发作模型的作用研究

Electroacupuncture promotes the efficacy of anti-seizure drugs in acute seizure models by enhancing the permeability of the blood-brain barrier

笪晓丽 1徐层林 2张小杰 1赵新月 1龚祎位 1仇肖允 1李立红 1王瑞明 1汪仪 2陈忠2

作者信息

  • 1. 浙江省神经药理学与转化研究重点实验室,浙江中医药大学附属第二医院(新华医院)针灸科,杭州 310053,浙江,中国
  • 2. 浙江中医药大学附属杭州市中医院(杭州市中医院)脑病科,杭州 310007,浙江,中国
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摘要

Abstract

Background:The blood-brain barrier(BBB)restricts the effective penetration of anti-seizure drugs(ASDs)into the brain,resulting in unwanted peripheral side effects of ASDs at therapeutic doses.Electroacupuncture(EA)has shown good efficiency in enhancing the drug molecules' permeability of BBB. Objective:We aimed to test the hypothesis that EA could improve the efficacy of ASDs for acute epileptic seizures by increasing their intracerebral concentrations. Methods:Firstly,quantitative analysis of electroacupuncture-mediated alterations in blood-brain barrier per-meability was performed involved two metrics:(1)Evans Blue penetration measured by the in vivo imaging system(IVIS)fluorescence imaging,and(2)brain tissue drug levels analyzed with high-performance liquid chromatography-mass spectrometry(HPLC)following intraperitoneal injection of ASDs,both experiments were performed after EA and intraperitoneal injection.Next,assessment of anti-seizure efficacy in models,as follow:post-electroacupuncture stimulation at GV20 and GV16,therapeutic and sub-doses of ASDs were delivered via intraperitoneal injection.Seizure susceptibility was evaluated using two distinct provocation methods:the clas-sic maximal electroshock tests and the pentylenetetrazol(i.p.)treatments,with seizure intensity being record.Lastly,the safety profile of electroacupuncture was preliminarily evaluated through open field test(OFT)and hot plate experiments. Results:We initially confirmed that EA was capable of enhancing the permeability of the BBB and increasing the intra-cerebral concentration of valproate acid.Then,behavioral experiments confirmed that EA combined with ASD exhibited superior efficacy compared to ASD monotherapy for acute seizures in both models.This enhancing efficacy could be extended to different ASDs with distinct acting mechanisms,including valproate acid,lamotrigine,lacosamide,and levetiracetam.And the electroacupuncture stimulation parameters were confirmed to be safe in mice through comprehensive behavioral evaluation. Conclusion:The results of the present study indicated that EA could improve the therapeutic efficacy of ASDs by enhancing the concentration of drugs in the brain,and provided a blueprint for better anti-seizure management with potential translational significance.

关键词

电针/抗癫痫药物/最大电休克/戊四唑/血脑屏障

Key words

Electroacupuncture/Anti-seizure drugs/Maximal electrical shock/Pentylenetetrazol/Blood-brain barrier

引用本文复制引用

笪晓丽,徐层林,张小杰,赵新月,龚祎位,仇肖允,李立红,王瑞明,汪仪,陈忠..电针通过提高血脑屏障通透性增强抗癫痫药对急性癫痫发作模型的作用研究[J].临床传统医学和药理学(英文),2025,6(4):57-66,10.

基金项目

This work was supported by grants from the National Natural Sci-ence Foundation of China(Nos.82374064,82173796)and the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04). (Nos.82374064,82173796)

临床传统医学和药理学(英文)

2097-3829

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