目的：通过对难治性癫痫患者外周血中多药耐药基因1（MDR1）、P 糖蛋白（P - gp）及谷胱甘肽 S 转移酶（GST - pi）的检测探讨难治性癫痫的发病机制；检测在不同发作类型、V - EEG 中癫痫样放电部位及用药方式的患者中此3项指标的水平。方法选取2012年3月—2013年3月贵州医科大学附属医院临床确诊的散发性的难治性癫痫患者31例（难治性癫痫组），另选择同期在本院接受抗癫痫药物控制良好的癫痫患者33例（治疗有效组），荧光定量法检测外周血 MDR1、GST - pi基因相对表达量，采用流式细胞术检测外周血 MDR1的表达产物P - gp的表达。结合临床特点与长程视频脑电图研究癫痫患者的发作类型、异常放电部位及用药方式，比较不同类型癫痫患者以上3项指标的表达情况。结果难治性癫痫组 MDR1、GST - pi基因相对表达量和白细胞P - gp高于治疗有效组，差异均有统计学意义（P ﹤0.01）。无论是治疗有效组还是难治性癫痫组，不同发作类型患者 MDR1、GST - pi基因相对表达量及白细胞P - gp比较，差异均无统计学意义（P ﹥0.05）。不同 V - EEG 异常放电患者 MDR1、GST - pi基因相对表达量及白细胞P - gp比较，差异均无统计学意义（P ﹥0.05）。不同用药方式患者 MDR1基因相对表达量比较，差异无统计学意义（P ﹥0.05）；不同用药方式患者GST - pi基因相对表达量和白细胞P - gp比较，差异均有统计学意义（P ﹤0.05），其中2种和3种用药方式GST - pi基因相对表达量均高于1种用药方式，3种用药方式白细胞P - gp高于1种和2种用药方式，差异均有统计学意义（P ﹤0.05）。结论癫痫患者外周血中GST - pi、P - gp或可成为难治性癫痫联合用药的耐药指标之一；癫痫患者外周血中 MDR1、GST - pi及P - gp与癫痫发作类型、癫痫样放电在 V - EEG 中的各种分布情况无明显相关性。%Objective To investigate the pathogenesis of refractory epilepsy by detecting the expression of MDR1, P - gp and GST - pi in peripheral blood of patients with refractory epilepsy and to detect the expression levels of the three indexes in patients with different types of epilepsy seizure,different epileptic discharge areas shown by V - EEG and different types of medication. Methods We enrolled 31 patients who were definitely diagnosed with sporadic refractory epilepsy in the Affiliated Hospital of Guizhou Medical University from March 2012 to March 2013 as the refractory group. Another 33 epilepsy patients who were treated well by antiepileptic drug in the same period were also enrolled as the effective group. Fluorescent quantitation method was employed to detect the change of relative gene expression of MDR1 and GST - pi in peripheral blood,and flow cytometry was employed to detect the expression of P - gp,an expression product of MDR1 in peripheral blood. Comparison was made in the expression of the three indexes among patients with different types of epilepsy in combination with clinical features,types of epilepsy seizure and abnormal discharge areas shown by long - term video EEG and different medications. Results Refractory group was higher(P ﹤ 0. 01)than effective group in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. The patients with different epilepsy seizure types in two groups were no significantly different( P ﹥ 0. 05) in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. Patients with different abnormal discharge areas shown by V - EEG were not significantly different(P ﹥ 0. 05)in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. Patients with different medications were not significantly different( P ﹥ 0. 05) in the gene relative expression of MDR1;patients with different medications were significantly different( P ﹤ 0. 05) in the gene relative expression of GST - pi and P - gp level of white cells,with patients taking 2 or 3 kinds of medicine higher(P ﹤ 0. 05)than patients taking 1 kind of medicine in the gene relative expression of GST - pi and patients taking 3 kinds of medicine higher( P ﹤ 0. 05) than patients taking 1 or 2 kinds of medicine in expression of P - gp of white cells. Conclusion GST - pi and P - gp in the peripheral blood of epilepsy patients may have the potential to become drug resistance indexes of the combined drug therapy for refractory epilepsy;the levels of MDR1,GST - pi and P - gp in the peripheral blood of epilepsy patients have no obvious relevancy with the type of epilepsy seizure and the various distribution of epilepsy discharge areas shown by V - EEG.
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