核因子-κB对癫痫大鼠脑P-糖蛋白表达的调控作用  

The regulation role of nuclear factor-kappa B on P-glycoprotein expression in the epileptic rat brain

作　　者：余年[1] 狄晴[1] 胡勇[1] 苏凌缨[1] 张燕芳[1] 蒋颖[1] 晏玉奎[1] 

机构地区：[1]南京医科大学附属脑科医院神经内科,210029

出　　处：《中国神经免疫学和神经病学杂志》2011年第1期5-9,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：南京市医学科技发展重大项目(2007-0211)

摘　　要：目的探讨核因子-κB(NF-κB)对癫痫大鼠脑P-糖蛋白(P-gp)表达的影响。方法将雄性SD大鼠随机分为假手术组(n=9)、癫痫组(EP组,n=14)、NF-κB活性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)干预组(PDTC组,n=14)。采用大鼠海马注射海人酸方法制作癫痫模型,PDTC组于癫痫造模前30 min给予腹腔注射PDTC(按体质量150 mg/kg)。于造模后24 h处死各组大鼠,采用免疫组织化学方法检测并比较各组大鼠海马CA3区、齿状回、嗅周皮层、杏仁核复合体区P-gp和NF-κB亚基p65(NF-κBp65)表达情况。结果与假手术组相比,EP组海马CA3区、齿状回、杏仁核复合体区P-gp和NF-κBp65表达显著增强(P<0.01),PDTC组P-gp和NF-κBp65表达低于EP组(P<0.01),且二者具有正等级相关性(P<0.05),而在嗅周皮层二者无相关性(P>0.05)。结论抑制NF-κB活化可以降低癫痫相关脑区P-gp过表达,癫痫发作所致脑内P-gp表达上调可能与NF-κB活化有关。Objective To investigate the effect of nuclear factor-kappa B （NF-κB） on P-glycoprotein （P- gp） expression in the brain of epileptic rats. Methods Male SD rats were divided into sham operation group （sham group, n =9）, epileptic group （EP group, n =14）, and NF-κB activity inhibitor-pyrrolidine dithiocarbamate salt （PDTC） intervened epileptic group （PDTC group, n=14）. The epilepsy was induced by kainic acid （KA） injection into the hippocampi and the PDTC group rats were given PDTC by intraperitoneal injection 30 min prior to KA （150 mg/kg）. Twenty-four hours after the operation, the rats were sacrificed. By Immuno-histochemical method, the expressions of P-gp and NF-κBp65 （the subunit of NF-κB） in hippocampus CA3 area, dentate gyrus, perirhinal cortex and amygdaloid nuclear complex were detected in each rat. Results Compared with the sham group, the expressions of NF-κBp65 and P-gp were significantly up-regulated in hippocampus CA3 area, dentate gyrus and amygdala complex in the EP group, however, the expressions of P-gp and NF-κBp65 were lower in the PDTC group than those in the EP group. There were statistically significant differences in NF-κBp65 and P-gp expressions among the three groups （P〈0. 01）. The expressions of NF-κBp65 and P-gp had positive rank correlation in hippocampus CA3 area, dentate gyrus and amygdala complex （P〈0.05）, whereas, no statistically significant correlation was found in perirhinal cortex （P〈0.05）. Conclusions Inhibition of NF-κB activation could block the up-regulation of P-gp in epilepsy-related brain and seizure-induced P-gp over-expression in epileptic brain may be related with NF-κB activation.

关 键 词：癫痫 海人酸 核因子-ΚB P-糖蛋白 海马 

分 类 号：R742.1[医药卫生—神经病学与精神病学]