目的：通过对难治性癫痫（intractable epilepsy，IE）患者外周血中多耐药基因（multidrug resistance 1， MDR1）、P糖蛋白（p glycoprotein，P-gp）及谷胱甘肽转移酶（glutathione transferaseπ，GST-Pi）的检测来探讨IE的发病机制；探讨这3项指标作为患者外周血标志物对临床治疗的指导意义。方法本研究分为3组，IE患者31例，抗癫痫药物（antiepileptic drugs，AEDs）控制良好者33例，健康者37例。采用荧光定量聚合酶链反应技术检测患者外周血中MDR1及GST-Pi的mRNA、流式细胞术检测患者外周血中MDR1的表达产物P-gp的表达。结果在MDR1基因与GST-Pi基因相对表达量方面，IE组（1.36±0.14，0.585±0.257）显著高于AEDs治疗有效组（0.82±0.15,0.309±0.217），（P＜0.05）；而AEDs治疗有效组又显著高于正常组（0.27±0.07,0.134±0.223），（P＜0.05）。在白细胞P-gp方面，IE组（0.104±0.084）显著高于AEDs治疗有效组（0.063±0.030），（P＜0.05）。在用药方式上，GST-Pi基因相对表达量方面，给予3种（0.535±0.256）及2种（0.425±0.254）AEDs联合治疗均显著高于给单药（0.267±0.265）治疗，（P＜0.05）；在白细胞P-gp方面，3种（0.141±0.096）AEDs联合治疗显著高于2种（0.071±0.020）AEDs联合治疗与单药（0.050±0.020）治疗，（P＜0.05）。结论癫痫患者外周血中的MDR1、P-gp及GST-Pi基因相对表达量或可作为IE的综合参考指标以及IE联合用药的耐药指标之一。%Objective The pathogenesis of intractable epilepsy was explored by examining the expression of the P-gp , GST-Pi as well as MDR1 in peripheral blood of the patients with intractable epilepsy. The potential of the above mentioned three genes as the biomarkers for treatment of intractable epilepsy was investigated. Methods Thirty-one sub⁃jects with refractory epilepsy, 33 subjects under good circumstances by antiepileptic drugs, and 37 healthy subjects were included in the present study. fluorescence quantitative polymerase chain reaction and flow cytometry were used to detect mRNA levels of MDR1 and GST-Pi and P-gp of MDR1 in the peripheral blood of the patients, respectively. Results The expression levels of MDR1 and GST-Pi were significantly higher in the AEDs intractable group(1.36±0.14,0.585±0.257) than in the treatment group(0.82±0.15,0.309±0.217, P<0.05)The expression levels of MDR1 and GST-Pi were signifi⁃cantly higher in the AEDs treatment group than in the normal group(0.27±0.07,0.134±0.223,P<0.05). The expression levels of P-gp were significantly higher in the AEDs of the intractable group(0.104±0.084)than in the treatment group (0.063 ± 0.030, P<0.05). The GST-Pi gene expression levels were significantly higher in three(0.535 ± 0.256)or two (0.425±0.254)kinds of antiepileptic drugs combination therapy than in single drug treatment(0.267±0.265, P<0.05). Leucocyte P-gp levels were significantly higher in combination therapy of three kinds of antiepileptic drugs(0.141 ± 0.096)than in combination therapy of two kinds of antiepileptic drugs(0.071±0.020)or in monotherapy(0.050±0.020, P<0.05). Conclusion MDR1 and GST-Pi gene expression levels of peripheral blood can be used as the reference in⁃dex for treatment of intractable epilepsy and the resistant index of combination treatment for intractable epilepsy.
展开▼
