细胞因子及免疫抑制剂对大鼠脑内神经递质的影响

Effects of cytokine and immunosuppressant on neurotransmitter in brain of rats

目的研究白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、戊四氮致痫和免疫抑制剂抗痫效应过程中谷氨酸(glutamate,Glu)和γ-氨基丁酸(γ-aminobutyric acid,GABA)在大脑皮质及海马内表达的变化,探讨IL-1β、IL-6在癫痫发病中的作用机制及免疫抑制剂的抗痫效应。方法将实验大鼠随机分为6组;即:对照组;IL-1β组;IL-6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。行侧脑室注射相应试剂120min后观察大鼠行为变化,并采用免疫组织化学方法检测大脑皮质及海马内Glu及GABA的表达变化。结果动物行为学观察,IL-1β组、IL-6组癫痫发作程度达中度;戊四氮组癫痫发作程度达重度。IL-1ra+戊四氮组癫痫发作较戊四氮组减轻,地塞米松+戊四氮组无明显癫痫发作。免疫组化染色显示,IL-1β组、IL-6组、戊四氮组Glu表达在大脑皮质及海马较对照组明显升高,GABA表达较对照组明显降低,差异具有显著性意义。IL-1ra+戊四氮组及地塞米松+戊四氮组与单独注射戊四氮组比较,Glu免疫染色减弱,GABA免疫染色增强,有显著性差异。结论IL-1β或IL-6可能通过升高Glu含量并降低GABA的含量参与致痫过程,从而使神经元兴奋性升高促进癫痫发作。免疫抑制剂具有抗痫效应。

Objective To study the changs of glutamic acid（Glu）and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1βor IL-6 or pentylenetetrazol（PTZ）. To explore the mechanism of IL-1β,IL-6 and immunosuppressant in epilepsy. Methods Experimental rats were randomly divided into 6 groups ： control group, IL-1β group, and IL-6 group, PTZ group, IL-1ra＋PTZ group,dexamethasone＋PTZ group. After intracerebroventricular injection of relevant agents for 120 min,behaviour changes were observed,Glu and GABA were examined by means of immunohistochemistry in the cerebral cortex and hippocampus of rats. Results The behaviour observation indicated that seizure in middle degree was observed in IL-1β group and IL-6 group and seizure in severe degree was observed in PTZ group. The seizure was lighter in IL-1ra＋PTZ group than in PTZ group. No seizure happened in dexamethasone＋PTZ and control group . Compared with control group, the immunoreaction of Glu showed that the expression was significantly increased in IL-1β group and IL-6 group and PTZ group,while GABA was obviously decreased. Compared with PTZ group,the immunostaining of Glu was significantly increased, and immunostaining of GABA was significantly decreased in IL-1ra＋PTZ group and dexamethasone＋PTZ group. Conclusion The maehanism of IL-1β or IL-6 particpated in promotion and induction epilepsy may be through increasing Glu and decreasing GABA in the cerebral cortex and hippoeampus. The nerve excitation is enhanced and then epilepsy occurs. The immunosuppressants could have anti-epilepsy effect.