NMDA受体1和雌激素受体在白细胞介素-2致痫大鼠脑内的表达变化和共存

THE STUDY OF EXPRESSION CHANGES AND COEXISTENCE OF NMDA RECEPTOR SUBMIT 1 AND ESTROGEN RECEPTOR IN THE BRAIN OF RATS WITH SEIZURE INDUCED BY IL-2

目的探讨白细胞介素2(IL-2)致痫与NMDA受体(NMDAR)和雌激素受体(ER)的关系。方法应用免疫组织化学、免疫荧光双标和激光共焦显微镜技术研究IL-2致痫大鼠及经免疫抑制剂预处理后再致痫大鼠脑内NMDAR-1、ER的表达变化以及NMDAR/ER和NMDAR/IL-2R共存情况。结果大鼠侧脑室注射IL-2以后,动物出现明显的癫痫发作,其大脑皮质和海马部位NMDAR-1及ER表达较对照组明显增多,免疫反应平均吸光度(A)值与对照组相比有极显著性差异;而用IL-2抑制剂环胞霉素(CsA)或糖皮质激素(G)预处理后再注射IL-2,动物未出现或仅出现轻微的癫痫发作,其NMDAR-1和ER表达较IL-2组明显减少(P<0.05)。研究还观察到大鼠脑内大脑皮质和海马部位NMDAR/ER或NMDAR/IL-2R之间存在着广泛共存。结论IL-2有致痫作用,NMDAR-1I、L-2R和ER在致痫活动中可能存在协同和互动作用。

Objective To explore the correlation between the epilepsy induced by interleukin-2 （IL-2） and changes of NMDA receptor （ NMDAR ） and estrogen receptor （ ER ）. Methods Methods of immunohistochemistry, double fluorescent immunohistochemistry and laser scanning confocal microscopy were applied to study the expression changes of NMDAR-1 and ER and the coexistence of NMDAR/ER and NMDAR/IL-2R in the brains of rats with epilepsy induced by IL-2 or rats treated with prior to the inducement. Results The rats displayed an obvious seizure after the lateral ventricle was injected with IL-2. The expressions of NMDAR-1 and ER were markedly increased and there was a significant difference in immunoreactive average absorbance （ A ） in cerebral cortex and hippocampus between IL-2 group and the control group. However, with the pretreatment of 1L-2 inhibitors, such as cyclosporine or glucocorticoid, the epileptic behaviors of rats with IL-2 were inhibited and the immunoreaction of NMDAR-1 and ER was obviously decreased compared with IL-2 group （P 〈 0.05）. It was also found that NMDAR/IL-2R or NMDAR/ER coexisted largely in cerebral cortex and hippocampus. Conclusion IL-2 could induce epilepsy. There exist cooperation and interaction between NMDAR-1, IL-2R and ER in epileptogenic mechanisms.