摘要
目的观察和探讨NF-κB信号传导通路抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)干预后戊四氮(PTZ)致痫大鼠海马Toll样受体4(TLR-4)表达和核转录因子κB(NF-κB转录)的变化,进一步研究TLR-4/NF-KB信号通路在癫痫发生发展过程中的作用机制。方法 SD大鼠45只,随机分为正常对照组(NS组)、癫痫模型组(PTZ组)和PDTC干预组(PDTC组),每组15只。PTZ组和PDTC组采用腹腔注射戊四氮制作大鼠慢性点燃模型,PDTC组在注射PTZ前60 min行腹腔注射PDTC,NS组注射等量的生理盐水,现察3组大鼠的行为学改变。28 d后断头迅速取脑,采用免疫组化方法检测海马组织CA1区NF-κB/p65表达的变化;同时用Western blotting检测海马组织TLR-4和NF-κB/p65蛋白的变化。结果与PTZ组相比,PDTC组癫痫发作级别明显减低,发作潜伏期延长。PTZ组大鼠NF-κB/p65阳性细胞数、NF-κB/p65蛋白表达水平均高于NS组和PDTC组,差异有显著性(P<0.05),PTZ组大鼠NF-κB/p65阳性细胞数、NF-κB/p65蛋白表达水平均高于NS组,差异有显著性(P<0.05)。PTZ组大鼠TLR-4蛋白表达水平均高于NS组和PDTC组,差异有显著性(P<0.05),PDTC组大鼠TLR-4蛋白表达水平均高于NS组,差异有显著性(P<0.05)。结论 NF-κB抑制剂PDTC对大鼠癫痫惊厥的干预作用可能与其抑制NF-κB/p65核转录,下调TLR-4表达有关。
[ Objective ] To investigate the influence of pyrrolidine dithiocarbamate （PDTC） on the expressions of Toll-like receptor 4 （TLR-4） and nuclear factor-κB （NF-κB） in hippocampus of status epileptic rats, and to explore the role of TLR-4/NF-κB signal pathway in the hippocampus injury of SE rats. [Methods] 45 SD rats were ran- domly divided into 3 groups with 15 rats each： saline （NS） group, pentylenetetrazole （PTZ） group and pyrrolidine dithiocarbamate （PDTC） group. The rats of FFZ group and PDTC group were injected with PTZ through intraperi- toneal, PDTC group were injected with PDTC 60 minutes before PTZ, NS group were injected with equivalent saline. The hippocampus were harvest on 28 d. The expression of NF-κB p65 protein in CA1 regions of rat hippocampus was detected by immunohistochemical staining, and The expression of NF-κB p65 and TLR-4 protein was detected by western blotting. [Results] Epileptic discharge was significantly decreased and seizure latency prolonged in PDTC group as compared with PTZ group. The positive cell count and the expression of NF-κB/p65 was significantly higher in PTZ group than in NS, PDTC group, the difference was significant（P 〈0.05）, and was higher in PDTC group than in NS group, the difference was significant （P 〈0.05）. The expression of TLR-4 was significantly higher in PTZ group than in NS, PDTC group, the difference was significant （P 〈0.05）, and was higher in PDTC group than in NSgroup, the difference was significant （P 〈0.05）. [ Conclusion ] The effect of PDTC on status epileptic, which might be associated with PDTC can suppress the nuclear transcription of NF-κB/p65 and down regulate the expression of TLR-4.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2013年第3期6-10,共5页
China Journal of Modern Medicine
