INTERLEUKIN-1 RECEPTOR IS A TARGET FOR ADJUNCTIVE CONTROL OF DIAZEPAM-REFRACTORY STATUS EPILEPTICUS IN MICE
INTERLEUKIN-1 RECEPTOR IS A TARGET FOR ADJUNCTIVE CONTROL OF DIAZEPAM-REFRACTORY STATUS EPILEPTICUS IN MICE
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INTERLEUKIN-1 受体是小鼠地西泮难治性癫痫持续状态辅助控制的靶点
DOI：
10.1016/j.neuroscience.2016.04.036
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Chen Zhong
中科院分区：
文献类型：
--
作者：
Xu Zheng-Hao;Wang Yi;Tao An-Feng;Yu Jie;Wang Xiao-Yu;Zu Yun-Yun;Zhang Shi-Hong;Chen Zhong
促炎细胞因子白细胞介素 1 β (IL-1β) 可能在癫痫持续状态期间在大脑中积聚，但其是否导致 SE 逐渐难治仍不清楚。通过使用红藻氨酸诱导的 SE 小鼠模型，我们测试了药物阻断或敲除 1 型白细胞介素 1 受体 (IL-1R1) 是否会影响长期 SE 的地西泮难治性现象。我们确认地西泮未能终止延长的 SE（允许在地西泮给药前持续 40 分钟）。长时间SE期间海马IL-1β的表达水平显着高于基线。有趣的是，在 IL-1R1 敲除小鼠中，延长的 SE 并不是地西泮难治性的。此外，白细胞介素-1受体拮抗剂（IL-1RA）与地西泮联合给药可终止已建立的延长SE，而单独使用IL-1RA不能终止延长SE。相反，给予重组人IL-1β会延长地西泮终止非延长SE的潜伏期，从而削弱地西泮的功效。因此，本研究提供了直接证据，表明积累的 IL-1β 导致了地西泮难治性长期 SE，并表明白细胞介素 1 受体是地西泮难治性 SE 辅助控制的靶点。
Proinflammatory cytokine interleukin-1 beta (IL-1β) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40 min before diazepam administration). The expression level of IL-1β in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1β weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1β contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE.