抗癫痫蛋白PRG-1能降低突触间的溶血磷脂酸（LPA）和谷氨酸神经递质水平而抑制癫痫复发。初始癫痫导致的海马区PRG-1 蛋白水平显著下降但mRNA表达不变，但是其机制完全不清楚。我们发现四种能结合PRG-1 3’UTR的miRNA (mir-221, -301b, -30a，-29c)表达量在癫痫动物海马区显著提高，因此推测它们可能抑制PRG-1 mRNA翻译而导致癫痫复发。我们计划：1）在细胞水平上检测这些miRNA能否抑制PRG-1 mRNA翻译；2）在癫痫小鼠中沉默这些miRNA或应用特异的LPA受体LPA2拮抗剂H2L5186303，然后检测是否影响：癫痫症状、海马区PRG-1 mRNA和蛋白水平、突触间LPA和谷氨酸水平、神经元的兴奋性、海马神经元损伤及癫痫复发频率及程度。本项目在理论上试图阐明一个新的导致癫痫复发的miRNA信号通路，并且在临床上提供一个新的治疗癫痫的方向。

The anti-epileptogenic protein PRG-1 can reduce the levels of synaptic lysophosphatidic acid (LPA) and glutamate neurotransmitter and thus suppress the recurrence of epilepsy. The level of PRG-1 protein in hippocampus induced by initial epilepsy was significantly decreased but its mRNA expression was unchanged, however, the molecular mechanism of PRG-1 protein decrease is completely unclear. We found that levels of four miRNAs (mir-221, -301b, -30a, -29c) capable of binding PRG-1 3'UTR were significantly increased in the hippocampus of epileptic animals, suggesting that they may suppress the translation of PRG-1 mRNA, eventually leading to the recurrence of epilepsy. We plan to: 1) test whether these miRNAs inhibit PRG-1 mRNA translation at the cellular level; 2) silence these miRNAs or apply the LPA receptor LPA2 antagonist H2L5186303 in epileptic animals, and measure whether this will affect: the symptoms of animal epilepsy, the level of PRG-1 mRNA and protein in hippocampus, levels of synaptic LPA and glutamate, and excitability of hippocampal neurons, the degree of neuronal apoptosis, and degree of oxidative stress and brain injury. This project theoretically attempts to elucidate a new miRNA signaling pathway that leads to the recurrence of epilepsy and to provide a new clinical direction for the treatment of epilepsy.