白金丸治疗多药耐药难治性癫痫的作用机制研究

项目名称： 白金丸治疗多药耐药难治性癫痫的作用机制研究

项目编号： No.81503559

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李静波

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 颞叶癫痫是成人难治性癫痫最为常见的类型，目前约有1/3癫痫患者在多种抗癫痫药联合治疗后仍不能有效控制，进展为难治性癫痫。古方白金丸具有豁痰通窍、清心安神的功效，临床运用抗癫痫疗效显著，尤其对难治性癫痫患者有治疗作用。近年受到多药耐药体及其作用机制的启示，发现多药转运体蛋白的过量表达参与了对多种抗癫痫药物的转运，从而导致癫痫耐药。本研究提出白金丸对难治性癫痫治疗的可能作用机制为调节多耐药基因及相关蛋白的表达调控，结合前期在离体海马切片上对癫痫样放电进行的研究基础，拟通过高效液相色谱法分析白金丸有效药物成分，并从整体癫痫动物模型行为学研究、离体海马切片电生理研究及受体蛋白分析三个层面探讨其在颞叶癫痫的发生发展中所起的作用、可能的电生理机制及多药耐药转运体机制。课题从中医药角度研究现代科学问题，有助于推动传统中药的科学探索，为难治性癫痫提供更多治疗选择。

中文关键词： 难治性癫痫；白金丸；多药耐药转运体；；P-糖蛋白；；多耐药基因相关蛋白1

英文摘要： Temporal lobe epilepsy is the most common type in adults with refractory epilepsy. There are about 1/3 of epileptic patients who can not be effectively controled by various antiepileptic drugs in combination therapy. They become refractory epileptic patients. Bai Jinwan has the effects of clearing phlegm and easing mental anxiety. Clinical effects of Bai Jinwan application to epilepsy is significant, especially the effect on the treatment of patients with refractory epilepsy. In recent years, by the enlightenment of the mechanism of multidrug resistance protein, expression of multidrug transporters in the brain of patients with epilepsy is in attention. For refractory epilepsy, overexpression and regulation of multidrug resistance related proteins, which participates in a variety of antiepileptic drug's transportion, leading to the epileptic drug-resistance. This study proposes that the possible mechanism of Bai Jinwan on treating refractory epileisy may be the regulation of expression of multiple drug resistance gene and related proteins. Based on the previous research of epileptiform discharges in isolated hippocampal slices, this study will analize the drug ingredients of Bai Jinwan by HPLC. And study the possible electrophysiological mechanisums and multiple drug resistance mechanisums by the behavior of overall epileptic model, electrophysiology of isolated hippocampal slices, and physiology of receptors. This research would study the modern scientific issues from the viewpoint of traditional Chinese Medicine, which would contribute to promoting the scientific exploration of traditional Chinese medicine, and provide additional treatment options for refractory epilepsy.

英文关键词： Refractory;Bai Jinwan;Multidrug resistance transporter ; P-glycoprotein;Multiple refractory protein 1