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苯妥英钠耐药性颞叶内侧癫痫大鼠模型的构建

Construction of rat model with phenytoin-resistant mesial temporal lobe epilepsy
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摘要 目的验证锂-匹罗卡品化学诱导及抗癫痫药物(AEDs)筛选构建的苯妥英钠耐药性颞叶内侧癫痫大鼠模型脑中AEDs浓度及多药转运蛋白表达。方法实验选取雌性6~8周SD大鼠30只,体重160~180 g(广东省实验动物研究所),采用锂-匹罗卡品化学诱导大鼠发生慢性颞叶内侧癫痫,视频脑电图(VEEG)监测苯妥英钠筛选期治疗效果,将颞叶内侧癫痫大鼠分成耐药性及不耐药性模型。采用活体微透析技术验证耐药性及不耐药性模型鼠脑中AEDs的浓度差异,免疫组织化学方法检测两组模型鼠脑中P糖蛋白的表达。结果有16只大鼠成功构建为慢性颞叶内侧癫痫模型,筛选出耐药模型大鼠6只(6/16)。苯妥英钠耐药性模型大鼠脑/血浆的时间药物浓度曲线的曲线下面积比值显著低于不耐药性模型大鼠(0.15±0.03 vs. 0.28±0.05,P<0.05)。苯妥英钠耐药性模型鼠较不耐药性模型鼠海马各区P糖蛋白表达明显增高(P<0.05)。结论苯妥英钠耐药性颞叶内侧癫痫大鼠脑中AEDs浓度低,可能与脑中P糖蛋白过表达有关。 Objectives The purpose of this study is to verify the phenytoin-resistant mesial temporal lobe epilepsy(MTLE) induced by Li-pilocarpine and screened by antiepilepsy drug(AEDs). Methods The rats with MTLE were induced by Li-pilocarpine, which were screened by effect of phenytoin treatment monitored by vedio-EEG. The living microdialysis technology was used for verification of drug concentration in brain of drug-resistant and drugresponsive rat model, and the P-glycoprotein expression was detected by immunohistochemical method. Results Sixteen rats with chronic MTLE were successfully induced in total 30 rats, among which, 6 drug-resistant rats with MTLE were screened. The brain/plasma ratio of area under the curve in drug-resistant rats was significantly lower than that of drugresponsive rats(0.15±0.03 vs. 0.28±0.05, P<0.05). In addition, the P-glycoprotein expression in brain of drug-responsive rats was obviously higher than that of drug-responsive rats(P<0.05). Conclusions The low concentration of phenytoin in drug-resistant rat model with MTLE was verified that might be related to the over-expressed P-glycoprotein in brain.
作者 方子妍 吴逢春 陈树达 秦家明 宁玉萍 周列民 FANG Ziyan;WU Fengchun;CHEN Shuda;QIN Jiaming;NING Yuping;ZHOU Liemin(Department of Neurology,the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital),Guangzhou 510370,China;Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders,Guangzhou 510370,China;Department of Neurology,the Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 518107,China;Department of Neurology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou,510080,China)
出处 《癫痫杂志》 2019年第1期21-25,共5页 Journal of Epilepsy
基金 国家自然科学基金(81801343、81701341、81571333、81071050、81571266、81771405) 广东省自然科学基金项目(2018A030313821) 广州市科技计划项目(201805010009、201807010064、201804010259、201709010043).
关键词 锂-匹罗卡品 颞叶内侧癫痫 耐药性癫痫 微透析 苯妥英钠 P糖蛋白 Li-pilocarpine Mesial temporal lobe epilepsy Drug-resistant epilepsy Microdialysis Phenytoin P-glycoprotein
作者简介 通信作者:宁玉萍,Eman:ningjeny@126.com;通信作者:周列民,Eman:lmzhou56@163.com.
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