基于GABA-AT/GAT-1对药“远志-天麻”治疗癫痫的机制研究

癫痫是一种由大脑神经元过度放电所引起的中枢神经系统功能失常的慢性病或综合征，机制仍不十分清楚。目前仍以化学药物治疗为主，但副作用明显，天然药物的作用和优势已引起学者的重视。研究表明，GABA能系统中的γ-氨基丁酸转氨酶（GABA-AT）、GABA转运体（GAT-1）及GABA受体功能异常是癫痫发病的关键原因，但其是否通过影响海马CA1与CA3区-颞叶投射调控癫痫发病尚不清楚。我们前期研究发现，对药“远志-天麻”提取物可以延长癫痫发作潜伏时间，但机制有待探讨。基于此，我们提出假说“‘远志-天麻’提取物可作用于海马CA1与CA3区GABA-AT/GAT-1调节突触前GABA传递，经海马-颞叶环路抑制颞叶神经元兴奋性而治疗癫痫”。本研究将以GAT-1敲除鼠制作模型，采用虚拟筛选、超滤离心质谱、光遗传等技术，系统阐明该对药治疗癫痫的机制，为中西医结合治疗癫痫提供科学依据。

Epilepsy is a chronic disease or syndrome of central nervous system dysfunction caused by excessive discharge of brain neurons with unclear pathogenesis up to date. Although applying anti-epileptic drugs (AEDs) is the primary therapy for the treatment of epilepsy, problems arise when using AEDs on symptoms, propelling researchers to seek natural medicine to cure or alleviate the symptoms of epilepsy because of its advantages. Recent studies have demonstrated abnormal functions of gamma-aminobutylase (GABA-AT), GABA transporter (GAT-1) and GABA receptor in the GABAergic system, etc., result in the morbidity of epilepsy, whereas it is still unclear that weather GABAergic system modulating the epileptic attack through the injection projections from the CA1 and CA3 areas in hippocampus to the temporal lobe area. Our previous research has indicated that extractions of herb pairs Polygala tenuifolia and Gastrodia elata inspired from the compatible theory in traditional Chinese medicine can effectively prolong the latent time of seizure to play a role in curing the epilepsy, but the molecular mechanism is unclear. Accordingly, we hypothesized that “extractions of herb pairs Polygala tenuifolia and Gastrodia elata can act on GABA-AT/GAT-1 in CA1 and CA3 areas of hippocampus to regulate presynaptic GABA transmission, and inhibit the excitability of temporal lobe neurons through hippocampal-temporal lobe circuit to treat epilepsy”.We plan to adopt a series of experimental methods including virtual screening and ultrafiltration centrifugal-LC-MS. In this way, we clarify the effect and mechanism systematically of herb pairs Polygala tenuifolia and Gastrodia elata therapy on curing epilepsy by modulating the presynaptic conduction of GABA and influencing projection between hippocampal and temporal lobe, providing evidence for the treatment of epilepsy through the perspective combining traditional Chinese and Western medicine.