IL-1β对L谷氨酸致痫大鼠大脑皮质和海马腺苷酸环化酶表达的影响

EFFECT OF IL-1βON THE VARIATION OF ADENYLYL CYCLASE EXPRESSION IN RATS WITH SEIZURES INDUCED BY L-GLUTAMATE

目的 探讨白细胞介素IL 1β促痫作用的机制及IL 1β对谷氨酸致痫大鼠大脑皮质和海马内腺苷酸环化酶表达的影响。方法 将实验SD大鼠随机分为生理盐水对照组 ;L Glutamate致痫组 ;IL 1β +L Glutamate组 ;IL 1ra +IL 1β+L Glutamate组 ;和MCCG (2 methyl 2 (carboxycyclopropyl) glycine) +IL 1β +L Glutamate组 ,每组 8只。采用行为学观察方法和免疫组织化学方法及Westernblot方法进行研究。结果 IL 1β +L Glutamate组大鼠癫痫发作的行为表现以及大脑皮质、海马内腺苷酸环化酶 (AC)表达与单纯用L 谷氨酸钠致痫大鼠组比较没有明显区别 (P >0 0 5 ) ,但与对照组比较AC表达增强 (P <0 0 5 ) ;如果预先给予IL ra,再给予IL 1β和阈下剂量的L 谷氨酸钠 ,癫痫发作不出现 ,脑内AC表达较对照组未见明显增强 (P >0 0 5 ) ;但如果预先给予MCCG ,脑内AC表达与对照组相比增高 ,癫痫发作的潜伏期最短 ,强度最大 ,与对照组比有显著性差异 (P <0 0 5 )。结论 本实验表明 :IL 1β有促痫作用 ,这种促痫效应的发挥可能与IL 1R介导的与谷氨酸受体的协同作用有关 ,并与AC表达增加有关。

Objective To explore the mechanism of interleukin-1beta (IL-1β) in the onset of seizure and the effect of IL-1β on the expression of adenylyl cyclase (AC) in rats with seizure induced by L-glutamate.Method Experimental rats were injected with IL-1βfirst and then L-glutamate (a dose under the threshold) into the right lateral ventricle and were sacrificed 4 hours after the onset of epileptic activity. The changes were examined by means of behaviour observation, immunohistochemistry and Western blotting and compared with those of rats with seizure induced by L-glutamate alone. Result We found that the expression of AC in the hippocampus and neocortex of rats with seizure induced by IL-1β and L-glutamate was stronger than that of the control group(P<0.05) but there were no remarkable differences between the L-glutamate group and IL-1β plus L-glutamate group in regard to the expression of AC, the latent period and the severity of seizure. If IL-ra was given (i.c.v.) first, there were no epileptic activities induced and the expression of AC did not increase. There wereno differencesin the expression of AC in rats with IL-1ra given first and that of the control rats. But IfMCCG was given (i.c.v.) first, the expression of AC was the strongest, with the shortestlatent period and the most serious seizure activities. Conclusion The results indicate that IL-1β can facilitatethe onset of epilepsy by L-glutamate through IL-1R, whilemetabotropicglutamate receptorsmay co-operate with IL-1R and the increased expression of AC may be involved in the process.