难治性癫与多药转运体关系的研究进展

Study Progress on Relationship between Intractable Epilepsy and Multidrug Transporter

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。

Epilepsy is a common nervous system seizure disease in children,20% -30% of them is intractable epilepsy. The pathogenesis of intractable epilepsy in children is not yet identify. Some research think that this may be associated with resistance of a variety of different mechanisms of antiepileptic drug and abnormalities of muhidrug resistance gene expression. The most investigation of multidrug transporter is P - glycoprotein, muhidrug resistance - associated protein. They are present in cell membrane and belong to adenosine triphosphate - dependent membrane transport protein. Studies have showed that over - expression of muhidrug transporter in temporal lobe brain tissue of patients with refractory epilepsy and animal model of chronic epilepsy reduce the concentration of therapeutic drug in ceils. They result in resistance by releasing the energy and transferring large amounts of anti - epileptic drugs to exterior of brain capillary endothelial cells in way of active transport. The relationship between muhidrug transporter＇s structure, distribution, functions and drug -resistant epilepsy are reviewed.