多药耐药基因在小儿难治性癫痫外周血中的表达及氟桂利嗪对其表达的逆转作用

Multidrug resistance gene expression in patients with refractory epilepsy and its reversal by flunarizine

目的探讨难治性癫痫患儿外周血中多药耐药基因(MDR1)的表达及氟桂利嗪在其辅助治疗中的作用。方法采用RT-PCR技术,检测MDR1在22例正常儿童和64例患儿辅助治疗前、后外周血中的表达情况,观察临床疗效和药物不良反应。结果难治性癫痫组未进行辅助治疗前MDR1 mRNA的表达水平明显高于正常对照组(P<0.01)。辅助治疗后,氟桂利嗪组MDR1 mRNA的表达低于安慰剂组(P<0.01),但高于正常对照组(P<0.05);安慰剂组MDR1 mRNA的表达比正常对照组高1.14倍,与辅助治疗前相比,氟桂利嗪组MDR1 mRNA表达水平降低(P<0.01),安慰剂组增高(P<0.05)。氟桂利嗪组与安慰剂组治疗有效率分别为55.56%和3.57%。氟桂利嗪不良反应发生率为8.33%。结论检测外周血MDR1 mRNA的表达可以评估难治性癫痫患儿对抗癫痫药物的敏感程度;氟桂利嗪对MDR1 mRNA的表达有逆转作用,能减轻癫痫的发作,且小剂量氟桂利嗪副作用小,耐受性好。

Objective To observe expression of MDR1 mRNA in peripheral blood and the tolerance of flunaxizine. Methods Expression of MDRI in the peripheral blood of 86 subjects was determined by PT-PCR. All subjects were divided into the refractory epilepsy （n=64） group and the control （n=22） group, and the refractory epilepsy group was sub-divided into the flunarizine treatment （ n = 36） group and the placebo treatment （ n = 28） group. MDR1 mRNA expression was re-examined with the same method. Results Expression level of MDR1 mRNA was elevated in the refractory epilepsy group compared with the control group （ P 〈 0.01）. After treatment with flunarizine for 7 to 8 weeks, 20 of 36 （55.56%） patients had good effects, but only 1 patient in the placebo group （3.57%） had an effect. Expression of MDR1 mRNA was decreased in the fltmarizine group but in- creased in the placebo group compared with the control group, also it was decreased in the flunarizine group and increased in the placebo group after treatments compared with the beginning of the experiments. Adverse effective rate was 8.33%. Conclusion Expression of MDR1 mRNA in peripheral blood is parallel to that in the brain, so it can be used to evaluate the sensibility of patients to drugs. Flunarizine is effective on refractory epilepsy with over-expression of MDR1 as an add-on therapy.