Tariquidar提高苯妥英钠在颞叶内侧癫痫模型鼠脑中的分布  

Effects of Tariquidar for Targeting Phenytoin into the Brain of MTLE Rat Model

作　　者：方子妍[1] 郭彩凤[1] 吴逢春[1] 秦家明 宁玉萍[1] 周列民[2] 

机构地区：[1]广州医科大学附属脑科医院/广州市惠爱医院神经科,广东广州510370 [2]中山大学附属第一医院神经科,广东广州510080

出　　处：《临床医学工程》2017年第6期762-764,共3页Clinical Medicine & Engineering

基　　金：国家自然科学基金面上项目(81071050;81571333);广州市医药卫生科技项目(20171A011268;20161A011036);广州市科技计划科技型中小企业创新-初创项目(2017010160496);广州市脑科医院广州市医学重点学科建设项目子项目(GBH2014-QN03)

摘　　要：目的观察tariquidar(TQD)能否避开颞叶内侧癫痫(MTLE)模型鼠P糖蛋白(Pgp)过表达的外排作用将抗癫痫药物输送至脑。方法锂-匹罗卡品诱导构建MTLE大鼠模型,并将模型鼠分成两组,分别予苯妥英钠(PHT)及PHT+TQD治疗,观察两组大鼠脑中PHT分布。活体微透析采集脑微透析液,高效液相色谱法检测PHT浓度。免疫组化检测Pgp表达。运用t检验或Wilcoxon秩和检验进行统计学分析。结果模型鼠海马区Pgp表达上调(P<0.05)。两组模型鼠的脑/血浆的时间药物浓度曲线的曲线下面积比值有显著性差异[PHT+TQD组(0.31±0.06)>PHT组(0.19±0.06),P<0.05]。结论 TQD可显著提高PHT在Pgp过表达MTLE模型鼠脑中的分布。Objective In order to evaluate that whether TQD has the ability of targeting of antiepileptic drug phenytoin into the brain with overexpression of Pgp in a model of mesial temporal lobe epilepsy （MTLE） rat. Methods The rats model of mesial temporal lobe epilepsy （MTLE） were induced by lithium-pilocarpine, which were divided into two groups with PHT and PHT ＋ TQD treatment, respectively. Dialysate samples were collected by microdialysis technology, and the analysis of samples was performed by high performance liquid chromatography （HPLC）. Immunohistochemistry assay was performed for Pgp expression at the hippocampus. The comparisons were carried out by t-test or Wilcoxon test. Results The Pgp immunopositive area was significantly higher in the hippocampus of MTLE rats when compared to the normal rats （P 〈0.05）. The significantly increased area under the curve （AUC） ratio of brain/plasma in PHT ＋ TQD drug group was 0.31 ± 0.06, when compared with PHT drug group （0.19 ±0.06）, P〈0.05. Conclusions TQD can significantly distribute PHT into brain with overexpressed Pgp in MTLE rat model.

关 键 词：颞叶内侧癫痫 匹罗卡品 P糖蛋白 TQD 耐药性癫痫 

分 类 号：R-332[医药卫生] R742.1