生酮饮食干预难治性癫痫相关信号通路的研究进展

Research Progress on Signaling Pathways Involved in the Intervention of Ketogenic Diet for Drug-Resistant Epilepsy

摘要: 癫痫是一种反复发作迁延难愈的神经系统疾病，目前治疗药物种类较多，但仍有30%难治性癫痫患者治疗效果不显著，生酮饮食已成为改善癫痫患者生活质量的重要方法，通过生酮饮食干预可调控多种信号通路，如AMPK/mTOR、谷氨酸-GABA平衡、Nrf2/HO-1、NF-κB、微生物–肠–脑(MGB)轴等通路干预癫痫发作，达到改善能量代谢、调节神经递质平衡、维持肠道菌群稳定、抗炎及抗氧化应激等作用。目前有较多关于生酮饮食抗癫痫作用机制的基础研究，但其确切作用机制尚未完全明确，本文对生酮饮食干预难治性癫痫相关信号通路的研究进展进行综述，探讨其治疗癫痫的作用机制。

Abstract: Epilepsy is a chronic and recurrent neurological disorder. Although a variety of antiepileptic drugs are currently available, approximately 30% of patients still experience drug-resistant epilepsy with inadequate therapeutic outcomes. The ketogenic diet has become an important approach to improve the quality of life in patients with epilepsy. Through ketogenic diet intervention, multiple signaling pathways can be regulated, including the AMPK/mTOR pathway, glutamate-GABA balance, Nrf2/HO-1 pathway, NF-κB pathway, and the microbiota-gut-brain (MGB) axis, to modulate epileptic seizures. This leads to improvements in energy metabolism, regulation of neurotransmitter balance, stabilization of intestinal microbiota, as well as anti-inflammatory and antioxidant effects. While numerous preclinical studies have explored the antiepileptic mechanisms of the ketogenic diet, its exact mechanisms of action remain incompletely understood. This article reviews recent advances in the signaling pathways associated with ketogenic diet intervention for drug-resistant epilepsy and discusses its therapeutic mechanisms.