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脑组织核因予#Kappa#B激活对实验性变态反应性脑脊髓炎的作用

檀国军, 杨天祝, 赵晓云, 周立霞, 曹翠丽, 马常升

河北医科大学神经生物研究室,病理生理研究室,石家庄。050017

摘要

为探讨脑组织核因子一KB( NF-KB)对实验性变态反应性脑脊髓炎(E AE)的作用,分别用凝胶电泳迁移分析和NF-KB p65免疫组化方法测定了CFA- GPSCH诱导大鼠EAE1 .7.14和21 d时脑组织NF-KB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-KB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-KB活性和蛋白表达量逐渐增高;在免疫后14 d达到高峰,NF-KB阳性细胞主要位于脉络丛、弯隆下器、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;21 d脑组织NF-KB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-KB特异性抑制剂PDTC以抑制脑内NF-KB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-KB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-KB的激活对EAE的发病起着关键的作用,应用NF-KB抑制剂可能是防治该病的有效方法之一。

关键词: 神经生物学; 脑脊髓炎; 凝胶电泳迁移分析; 核因子一KB; 弯隆下器

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

TAN Gua Jun, YANG Tiair Zhu, ZHAO Mao yun, ZHOU Li-Ma, CAO Cur Li, MA Chang Sheng

Department of Neurobiology and Pathophysiology, Hebei Medical University, Shijiazhuang 050017

Abstract

To investigate the role of activated nuclear factorxB(NF-KB) in experimental allergic encephalo myelitis(E AE),the activity and protein expression of NF-KB p65 in rat brain tissues,which were extracted from EAE rats at 1,7,1 4 and 21 d respectively after EAE was induced by CFA- GPSCH,
were measured with electrophoretic mobility shift assay and unohistochemistry.The relationship Setween activated NF-KB and symptoms of EAE was also investigated.The results showed that protein expression level and the activity of NF-KB were very low in the brain of the control group .After EAE was induced,the activity of NF-KB 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-KB 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-KB 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-KB,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-KB were in parallel with the changes in symptoms and pathological lesion of EAE rat brains .In conclusion,the activated NF-KB in the brain may play a critical role in the pathogenesis of EAE,and application of some inhibitors of NF KB,such as PDTC,may be one of the effective therapeutic methods for prevention and treatment of EAE.

Key words: neurobiology;encephalo myelitis;electrophoretic mobility shift assay;NF kappa B;subfornical organ

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引用本文:

檀国军, 杨天祝, 赵晓云, 周立霞, 曹翠丽, 马常升. 脑组织核因予#Kappa#B激活对实验性变态反应性脑脊髓炎的作用[J]. 生理学报 2003; 55 (1): .

TAN Gua Jun, YANG Tiair Zhu, ZHAO Mao yun, ZHOU Li-Ma, CAO Cur Li, MA Chang Sheng. The role of activation of nuclear factor kappa B of rat brain in the pathogenesis of experimerntal allergic encephalomyelitis . Acta Physiol Sin 2003; 55 (1): (in Chinese with English abstract).