癫痫患儿外周血多药耐药基因动态表达及其意义研究

The dynamic expression and significance of multidrug resistance gene in the peripheral blood of children with epilepsy.

目的研究癫痫患儿外周血多药耐药基因1(MDR1)表达动态变化,探讨其与癫痫耐药的关系及预测儿童抗癫痫药物(AEDs)疗效的价值。方法选取2011年1月至2012年7月重庆医科大学附属儿童医院神经内科门诊和病房就诊的难治性癫痫患儿30例、初诊癫痫患儿40例及健康体检儿童30例,分别于入组前、治疗后6、12和18个月,应用逆转录聚合酶链反应(RT-PCR)半定量法检测外周血MDR1mRNA的表达,分析MDR1表达及其表达水平与癫痫发作频率和应用AEDs抗癫痫疗效的关系。结果难治性癫痫组、初诊癫痫组入组前,治疗6、12、18个月MDR1表达较对照组均显著增高(P<0.01);难治性癫痫组各个观察时间点MDR1表达较初诊癫痫组显著增高(P<0.01);难治性癫痫组MDR1表达治疗18个月较入组前明显增高,治疗6个月及12个月(P<0.05),治疗12个月较入组前及治疗6个月(P<0.05);初诊癫痫组各个观察时间点MDR1的表达比较差异无统计学意义(P>0.05)。难治性癫痫组入组前MDR1表达阳性19例中16例(84.2%)治疗无效,表达阴性11例中3例(27.3%)无效,两者比较差异有统计学意义(P<0.01);初诊癫痫组入组前MDR1表达阳性13例中9例(69.2%)转化为难治性癫痫,表达阴性27例中2例(7.5%)转化为难治性癫痫,两者比较差异有统计学意义(P<0.01)。发作频繁患儿MDR1水平明显高于发作较少患儿(P<0.01);使用4种AEDs患儿MDR1水平明显高于使用2种及3种AEDs(P均<0.01)。结论癫痫患儿外周血MDR1表达升高,难治性癫痫升高更明显,可能是临床耐药的原因,可作为评估AEDs疗效的观察指标。

Objective To observe dynamic changes of the expression of multidrug resistance gene 1 （MDR1） in peripheral blood of children with epilepsy, and to explore the relationship between it and epileptic resistance and its value of predicting efficacy of antiepileptic drugs （AEDs）.Methods Thirty children with refractory epilepsy, forty newly diagnosed epilepsy and thirty healthy children were collected. The expression of MDRlmRNA was analyzed by reverse transcription polymerase chain reaction （RT- PCR）semi-quantitatively before entering group, 6 months, 12 months and 18 months after treatment, respectively.The relationship of MDR1 level with epileptic frequency and therapeutic effect of AEDs was analyzed.Results The expression of MDR1 in refractory epilepsy group and newly diagnosed epilepsy group at every time point was all significantly higher than that in healthy control group （P 〈 0.01 ）.The expression of MDR1 in refractory epilepsy group at every time point was significantly higher than that in newly diagnosed epilepsy （P 〈 0.01）. There was a significant difference on the expression of the MDR1 in refractory epilepsy group at every time point （P 〈 0.01, P 〈 0.05）and no significant difference in newly diagnosed epilepsy group. In refractory epilepsy group before enter- ing group, 16 of 19 cases （84.2%）with over expression of MDR 1 became invalid , 3 of 11 cases （27.3%）without expression of MDR1 became invalid, and there was a significant difference between them （P〈 0.01）.In newly diagnosed epilepsy group before entering group, 9 of 13 cases （69.2%）with over expression of MDR1 became intractable epileptic patients and 2 of 27 （7.5%） without expression of MDR1 became intractable epileptic patients, and there was a significant difference between them （P〈 0.01 ）. MDR1 expression was more among patients with high frequent epilepsy than patients with low frequent epilepsy （P 〈 0.01）.MDR1 expression was more in patients administered with four kinds of AEDs than those with two or three kinds of AEDs （P 〈 0.01）.Conclusion The expression of MDR1 increases in peripheral blood of children with epilepsy, espeially in refractory epileptic children. The increased expression of MDR1 may play an important role in clinical drug resistance. The expression of MDR1 may be a predictable marker in evaluating efficacy of AEDs.