核因子κB在大鼠脑缺血耐受中的作用及其对细胞间黏附分子-1和Bcl-2表达的影响

The effect of nuclear factor κB on expression of intercellular adhesion molecule-1 and Bcl-2 and its role in cerebral ischemic tolerance of rats

目的 探讨核因子κB(NFκB)在大鼠脑缺血耐受中的作用及其可能的参与途径。方法 建立大鼠 4血管闭塞的全脑缺血耐受模型 ,将实验动物随机分为 4组 :假手术组 (sham) ,缺血再灌注组 (I/R) ,缺血预处理加缺血再灌注组 (IP +I/R) ,DTTC(NFκB的特异性抑制剂 )加缺血预处理组加缺血再灌注组 (IPDTTC+I/R)。用凝胶电泳迁移率改变分析法检测NFκB的活性 ,免疫组化技术检测细胞间黏附分子 1(ICAM 1)和Bcl 2的表达。结果 I/R中NFκB被激活 ,IP可抑制其激活 ,DTTC可逆转IP对I/R中NFκB的抑制效应 ;IP +I/R组与I/R组相比 ,神经元计数明显增高 ,ICAM 1的表达降低 ,Bcl 2的表达增加 ;给予DTTC处理后 ,IP的神经保护作用明显减弱 ,IPDTTC+I/R组与I/R组ICAM 1和Bcl 2的表达无显著性差异。结论 IP的神经保护效应依赖于NFκB的激活 ,可能部分通过上调Bcl 2的表达 ,同时抑制I/R中NFκB的活性而减少ICAM 1的产生发挥作用。

Objective To study the role and possible pathway of nuclear factor κB (NFκB) in cerebral ischemic tolerance of rats. Methods Rats were randomly divided into four groups:(1)shamed operation (sham);(2)ischemic and reperfusion (I/R);(3)IP followed by I/R (IP+I/R);(4)IP in the presence of DTTC followed by I/R(IP DTTC+I/R). The neuronal density of hippocampi,expression of intercellular adhesion molecule-1(ICAM-1) and Bcl-2,and NFκB activation were determined. Results In preconditioned rats (IP+I/R),the neuronal density of hippocampi and expression of Bcl-2 were significantly increased compared with both I/R alone and IP DTTC+I/R groups (P< 0.01),and expression of ICAM-1 was significantly decreased compared with them (P< 0.01). Electrophoretic mobility shift assays(EMSA)showed NFκB activation with I/R that was blocked by IP. I/R alone and IP DTTC+I/R groups showed NFκB activation with I/R that was absent in preconditioned rats. Conclusion The cytoprotective effects induced by IP require activation of NFκB,partly by changes of expression of ICAM-1 and Bcl-2.