儿童难治性癫(癎)外周血P糖蛋白的表达及药物干预

目的 测定儿童难治性癫(癎)及初诊癫(癎)患儿外周血白细胞多药耐药基因产物P糖蛋白(P-gp),建立儿童难治性癫(癎)耐药性客观指标及预测儿童难治性癫(癎)客观指标;同时观察氟桂利嗪的疗效.方法 应用流式细胞仪检测41例难治性癫(癎)儿童及45例初诊癫(癎)儿童外周血多药耐药基因产物P-gp的表达,44例健康儿为对照组.难治性癫(癎)组患儿加用氟桂利嗪(弗瑞林)2.5～5 mg,qn口服治疗,对其疗效进行临床验证.结果 难治性癫(癎)组P-gp表达阳性23例(56.1%),初诊癫(癎)组P-gP表达阳性10例(22.2%),对照组P-gp表达阳性3例(6.8%),三组比较差异有统计学意义(X2=26.77,P(0.01).难治性癫(癎)组与对照组比较X2=24.27,P<0.01;难治性癫(癎)组与初诊癫痫组比较X2=10.41,P<0.01;初诊癫痫组与对照组比较X2=4.23,P<0.05.难治性癫痫组P-gp表达阳性23例中17例(73.9%)无效,6例(26.1%)有效,P-gP表达阴性18例中3例(16.7%)无效,15例(83.3%)有效,两者比较差异有统计学意义(X2=10.10,P<0.01).初诊癫痫组P-gp表达阳性10例中7例(70.0%)转为难治性癫(癎),P-gp表达阴性35例中3例(18.6%)转为难治性癫(癎).两者比较差异有统计学意义(X2=16.98,P<0.01).难治性癫(癎)组抗癫(癎)药物治疗无效者20例加用氟桂利嗪治疗3个月,P-gP表达阳性17例中有效11例(64.7%),11例有效者复查P-gP有6例(54.5%)转为阴性;无效6例(35.3%),复查P-gP表达仍阳性.P-gP表达阴性3例中1例有效,2例无效,复查P-gp表达阴性.结论 外周血多药耐药基因产物P-gP在儿童难治性癫(癎)中表达增强,可作为儿童难治性癫(癎)耐药性的客观指标;P-gP表达阳性的初诊癫(癎)患儿多转为难治性癫(癎),P-gP可作为预测儿童难治性癫(癎)的客观指标;氟桂利嗪有一定抗癫(癎)及逆转P-gP的表达作用.

P-glycoprotein in peripheral blood of children with intractable epilepsy and drug interference

Objective To explore the relationship between expression of P-glycoprotein (P-gp), a product of multidrug resistance (MDR) gnne, in the peripheral blood of children with intractable or newly diagnosed epilepsy for drug resistance. To establish a marker of drug resistance. To evaluate the therapeutic effect of flunarizine in the treatment of intractable epileptic patient with or without overexpression of P-gp. Methods The expression of P-gp in peripheral blood were investigated in 86 epileptic children (41 in intractable epilepsy group, 45 in newly diagnosed epilepsy group) and 44 healthy children (controlled group) by flow cytometry. Intractable epileptic patients with or without overexpression of P-gp were given flunarizine 2.5 - 5 mg, po, qn, for 3 months and followed up. Results Overexpression of P-gp were found in 23 (56.1%) patients of intractable epilepsy group, in 10 (22.2%) patients of newly diagnosed epilepsy group and three (6.8%) children of the controlled. In intractable epilepsy group, 17 out of 23 cases (73.9%) patient with overexpression of P-gp became tolerant to antiepileptic drugs, while 3 out of 18 cases (16.7%) patient without expression of P-gp became tolerant to antiepileptic drugs, and there was significant difference between them (P < 0.01) . In the newly diagnosed epilepsy group, seven out of 10 cases (70%) with overexpression of P-gp became intractable epileptic patient and three out of 35 eases (18.6%) without expression of P-gp became intractable epileptic patient, there was significant difference between them (P < 0.01). Twenty patients of intractable epilepsy group were given flunarizine for three months, 11 of 17 patients with P-gp overexpression and 1 of 3.patients without P-gp expression were effective. When reexamined, P-gp expression in 6 out of 11 patients became negative. Conclusions It is suggested that overexpression of P-gp in the peripheral blood of intractable epileptic patients might be a significant marker of drug resistance. Newly diagnosed epileptic patients with overexpression of P-gp may develop intractable epilepsy. P-gp was a predictable marker of intractable epilepsy. Flunarizine could be a choice in treatment of intractable epilepsy with overexpression of P-gp. The antiepileptic mechanism of flunarizine may involve in reversing of P-gp.