NF-κB在发育鼠戊四氮反复点燃癫痫形成中的作用

Role of NF-κB in pentetrazole-induced repeated seizure in developing rats

目的:用NF-κB阻滞剂吡咯烷二硫基甲酸盐(PDTC)阻断NF-κB的表达,探讨核因子κB(NF-κB)在发育鼠戊四氮(PTZ)点燃癫痫形成过程中的作用。方法:生后10 d(P10)Wistar大鼠72只,随机分为PTZ组、PDTC+PTZ组及生理盐水对照组3组,制备戊四氮反复点燃癫痫模型。观察各组大鼠行为学改变、海马各区细胞形态及细胞计数、NF-κB表达、5-溴-2-脱氧尿嘧啶核苷(BrdU)阳性细胞数和苔藓纤维发芽等指标。结果:(1)NF-κB表达,PTZ组显著高于对照组及PDTC+PTZ组(P<0.01);(2)海马神经细胞计数,PTZ组齿状回(DG)区颗粒细胞较对照组显著增加(P<0.05);PDTC+PTZ组CA1、CA3和门区神经元数较PTZ组均明显减少(P<0.05);(3)DG区BrdU阳性细胞数,PTZ组和PDTC+PTZ组均较对照组显著增加(P<0.01);PDTC+PTZ组DG区BrdU阳性细胞数目明显较PTZ组少(P<0.01);NF-κB吸光度值与BrdU阳性细胞数/颗粒细胞数相关性分析呈正相关,具有统计学意义(P<0.01);(4)苔藓纤维发芽,PDTC+PTZ组和PTZ组均有苔藓纤维发芽,两组比较没有显著差异。结论:NF-κB在发育鼠癫痫中发挥重要作用,促进海马神经元发生,保护海马神经细胞,但对苔藓纤维发芽无明显作用。

AIM： To investigate the role of NF - κB in pentetrazole - induced repeated seizure in developing rats with the inhibitor of NF - κB pyrrolidine dithiocarbamate （PDTC）. METHODS： 10 -day -old Wistar rats （n = 72） were prepared for epilepsy model and divided into three groups at random： the PTZ group, the PDTC ＋ PTZ group and the control group. The behavioral changes, the cells morphology and neurons counts in hippocampus, the expression of NF - κB, BrdU （5 - bromo, 2 - deoxyuridine） immunoreactive cells in hippocampus and the mossy fiber sprouting were observed. RESULTS： （ 1 ） The NF - KB expressed in PTZ group was significantly higher than that in PDTC ＋ PTZ group and control group （P 〈0. 01 ）, （2） The dentate gyrus granule cell count in PTZ group was significantly higher than that in control group （ P 〈 0. 05 ）, In PDTC ＋ PTZ group cell counts in CA1, CA3 and hilar region were significantly lower than those in PTZ group （ P 〈 0. 05 ）. （ 3 ） The BrdU - immunoreactive cells counts in dentate gyrus in PTZ group and PDTC ＋ PTZ group were significantly higher than those in control group （P 〈 0, 01 ）, but in PDTC ＋ PTZ group BrdU -immunoreactive cell count was significantly lower than that in PTZ group （P 〈 0, 01 ）. Correlate analyzes between NF - κB expression and BrdU- immunoreactive cell counts/granule cell counts showed positive correlation （P 〈 0.01 ）. （4） The mossy fiber sprouting in both PTZ and PDTC ＋ PTZ group was observed, However, the degrees of sprouting showed no significant differences between two groups. CONCLUSION： NF - κB plays a crucial role in epilepsy of developing rats. It encourages neurogenesis and protects neurons in hippocampus, but has no significant effect on mossy fiber sprouting.