白介素17A在癫痫发生中的作用及其机制研究

免疫异常在癫痫发生发展中的作用日益受到重视。白介素17A（IL-17A）是新发现的高效促炎因子，可促进自身免疫系统疾病的发生和发展。我们前期研究发现，癫痫患者外周血PBMC分泌IL-17A水平是癫痫发作严重程度的独立危险因素，并发现颞叶癫痫患者脑组织中有IL-17受体表达，表明IL-17A在癫痫发病中可能发挥了重要的作用。在前期研究的基础上，我们将进一步比较IL-17受体敲除小鼠和野生型小鼠在匹鲁卡品致痫后癫痫的发作严重程度、血脑屏障破坏情况及IL-17A动态变化，探讨IL-17A在癫痫发病中的作用；采用海马脑片培养，给予RNA干扰，分析阻断IL-17A通路对神经元放电的影响以及相应受体通路变化，阐明IL-17A在癫痫发生发展的途径。在此基础上，采用蛋白转导技术将IL-17受体抗体导入神经细胞，评估治疗癫痫新的免疫学治疗途径可行性。本项目的实施有望建立治疗癫痫新的免疫学途径。

Epilepsy is a chronic neurologic disorder in which immunological factors are thought to play a crucial role. IL-17A has been characterized as a pleiotropic inflammatory cytokine, and plays a pathological role in the development of inflammatory diseases and correlates with disease severity.Our study report the first clinical evidence for elevated IL-17A levels in the peripheral blood and CNS in epilepsy patients and demonstrated the expression of IL-17R in the temporal lobe of epilepsy patient. We further showed that IL-17A level is an independent factor of seizure severity. Our findings cast a light on a new therapeutically potential of IL-17A in epilepsy..Therefore, we will explore the effect and pathway of IL-17A in epilepsy based on our results. First, we will compare the seizure severity, destruction of blood-brain barrier and dynamic change of IL-17A levels in pilocarpine model with IL-17 receptor knockout mice and wild-type mice to identify the possible role of IL-17A in the development and progression of epilepsy. We will also explore the changes of neuronal discharge and corresponding receptor pathway changes after blocking IL-17A pathway by RNA interference on cultured hippocampal slices to study the possible pathway of IL-17A. Then,we will use protein transduction domains to translocate IL-17R across the plasma membrane of neuron cells into cytoplasm, to look for a new immunological direction for the strategy of seizure control.Our findings cast a light on a new therapeutically potential in epilepsy.