脑组织核因子-κB激活对实验性变态反应性脑脊髓炎的作用

The role of activation of nuclear factor-kappa B of rat brain in the pathogenesis of experimental allergic encephalomyelitis

为探讨脑组织核因子 κB(NF κB)对实验性变态反应性脑脊髓炎 (EAE)的作用 ,分别用凝胶电泳迁移分析和NF κBp65免疫组化方法测定了CFA GPSCH诱导大鼠EAE 1、7、14和 2 1d时脑组织NF κB活性和蛋白表达的动态变化 ,并观察了这些变化与EAE症状之间的关系。结果显示 :对照组大鼠脑组织仅有少量NF κB蛋白表达 ,其活性也很低 ;诱导EAE后 ,伴随着大鼠EAE症状及脑组织病理损伤的出现和进行性加重 ,其NF κB活性和蛋白表达量逐渐增高 ;在免疫后 14d达到高峰 ,NF κB阳性细胞主要位于脉络丛、穹隆下器、血管“套袖样”病灶的周围 ,与EAE病变部位一致 ,此时大鼠EAE发病率最高、病情最重、体重减轻最显著、脑组织病理改变也最明显 ;2 1d脑组织NF κB活性和蛋白表达量逐渐下降 ,大鼠EAE症状也逐渐恢复。应用NF κB特异性抑制剂PDTC以抑制脑内NF κB蛋白表达后 ,大鼠EAE症状和脑组织损伤明显减轻 ,说明脑组织NF κB的动态变化与EAE症状及脑组织损伤程度密切相关。结论 :脑组织NF κB的激活对EAE的发病起着关键的作用 ,应用NF κB抑制剂可能是防治该病的有效方法之一。

To investigate the role of activated nuclear factor κB (NF κB) in experimental allergic encephalomyelitis (EAE), the activity and protein expression of NF κB p65 in rat brain tissues, which were extracted from EAE rats at 1, 7, 14 and 21 d respectively after EAE was induced by CFA GPSCH, were measured with electrophoretic mobility shift assay and immunohistochemistry. The relationship between activated NF κB and symptoms of EAE was also investigated. The results showed that protein expression level and the activity of NF κB were very low in the brain of the control group. After EAE was induced, the activity of NF κB and the level of the protein expression in the brains increased gradually with the development of symptoms and brain pathology of EAE. On d 14, both the activity and the level of protein expression in the brains reached a peak, the positive cells of NF κB were mainly located at the choroid plexuses and subfornical organ, as well as around the regions of 'sleeve like' lesion foci, which were coincident with the locations of lesions of EAE. The incidence, symptoms, reduction of the body weight and pathology of EAE rats brains at the above locations were most significant. On d 21 the activity of NF κB and level of the protein expression reduced gradually, which was in parallel with a gradual alleviation of the symptoms of EAE rats. After a specific inhibitor of NF κB, PDTC was applied, the symptoms and pathological lesions of EAE rat brain were mitigated markedly. The above results indicate that the dynamic changes in the activity and protein expression of NF κB were in parallel with the changes in symptoms and pathological lesion of EAE rat brains. In conclusion, the activated NF κB in the brain may play a critical role in the pathogenesis of EAE, and application of some inhibitors of NF κB, such as PDTC, may be one of the effective therapeutic methods for prevention and treatment of EAE.