白细胞介素-1β对水通道蛋白4表达的影响及其在癫痫发作中的作用

Effects of IL-1β on expression of AQP4 and its role in attack of seizure

目的:观察白细胞介素-1β(IL-1β)和戊四氮致急性癫痫大鼠大脑海马水通道蛋白4(AQP4)表达变化,探讨IL-1β调节AQP4表达参与癫痫发病的作用机制。方法:将大鼠随机分为5组,对照组、IL-1β组、戊四氮组、IL-1ra(IL-1受体拮抗剂)+戊四氮组、地塞米松+戊四氮组。记录60 min内各组大鼠痫性发作级别。免疫组织化学、RT-q PCR检测6、12、24、36 h海马AQP4的表达。结果:IL-1β组和戊四氮组重度癫痫发作;地塞米松+戊四氮组和对照组无明显发作;IL-1ra+戊四氮组较戊四氮组发作减轻(P<0.05)。免疫组化和荧光定量PCR显示:戊四氮组与对照组相比12 h后AQP4表达明显升高(P<0.05),发作后24 h达到高峰(P<0.001),IL-1ra+戊四氮组12～36 h的AQP4表达都低于戊四氮组同时间点(P<0.05),地塞米松+戊四氮组与对照组相比无统计学意义(P>0.05)。结论:促炎因子IL-1β可能通过上调海马AQP4表达,影响脑内局部水平衡,增加细胞外兴奋性氨基酸或离子的浓度,促进神经元放电。

Objective To observe the effects of interleukin-1β（IL-1β） and pentylenetetrazol（PTZ）induced acute epilepsy and the dynamic expression of aquaporin-4（AQP4） in hippocampus. To explore the role of IL-1β in the pathogenesis of epilepsy by regulating AQP4. Methods All rats were randomly divided into control group, IL-1β group, PTZ group, IL-1ra ＋ PTZ group and dexamethasone ＋ PTZ group. Observe the behavior of the rats within 60 minutes after injection and record seizure score in each group. Then immunohistochemistry and RT-q PCR were used to detect the expression of AQP4 at at 6, 12, 24 and 36 h.Results Almost of rats in IL-1β group and PTZ group showed severe degree seizure. The rats in control group and dexamethasone ＋ PTZ group showed no obvious seizure. The seizure of rats were more remarkable serious in PTZ group than that in the IL-1ra ＋ pentylenetetrazole group（P〈 0.05）. Immunohistochemistry and RT-q PCR Show： the expression of AQP4 in hippocampus in PTZ group increased gradually after 12 h（P〈 0.05）, then reached in the peak after 24 h（P〈 0.001）. The expression of AQP4 in IL-1ra ＋ PTZ group was lower compare with PTZ group in each time（P 〈0.05）. Although the expression of AQP4 in dexamethasone ＋ PTZ group higher than the control group, it was not significantly different（P 〈0.05）. Conclusion The proinflammatory cytokine IL-1β break the balance of water in brain and increasing the concentration of extracellular excitatory amino acids or ions by upregulate the expression of AQP4 in order to promote the excitatory of neurons.