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儿童癫是儿科神经系统常见的一种发作性疾病,其中20%～30%为难治性癫(IE)。儿童IE的发病机制尚不明确,国内外研究认为可能与不同作用机制的多种抗癫药耐药有关,与多药耐药基因表达异常有关。目前研究多药转运体抗癫药物耐药机制最多的有p糖-蛋白、多药耐药相关蛋白,二者是存在于细胞膜上的蛋白质超家族,属于ATP依赖的膜转运蛋白。研究显示IE患者颞叶脑组织及慢性癫动物模型中p糖-蛋白、多药耐药相关蛋白等多药转运体过度表达,它们通过利用分解ATP所释放的能量,以主动转运的方式将大量抗癫药物转运到大脑毛细血管内皮细胞之外,降低治疗药物在细胞内的水平,从而产生耐药。现就多药转运体的结构、分布、功能及其与癫耐药的关系作一综述。
Childhood epilepsy is a common disease of the pediatric nervous system, of which 20% to 30% of refractory epilepsy (IE). The pathogenesis of children with IE is not yet clear, domestic and foreign studies that may be related to different mechanisms of action of a variety of anti-epileptic drug resistance, and multidrug resistance gene expression abnormalities. At present, there are p-glycoprotein and multidrug resistance-related proteins that have the most mechanism of resistance to multi-drug transporter antiepileptic drugs. They are both protein superfamilies that exist on the cell membrane and belong to ATP-dependent membrane transporters. Studies have shown that over-expression of p-glycoprotein, multidrug resistance-associated protein and other multi-drug transporter in temporal lobe brain tissue and chronic epileptic animal model in IE patients, through the use of energy released by the decomposition of ATP, A large number of antiepileptic drugs transport to the brain capillary endothelial cells, reducing the level of therapeutic drugs in the cell, resulting in drug resistance. Now on the structure of multi-drug transporter, distribution, function and its relationship with epilepsy drug resistance are reviewed.