IKKβ抑制剂对肌萎缩侧索硬化症的保护性作用
Protective effects of IKKβ inhibitor on amyotrophic lateral sclerosis
刘亚坤 1温迪 1祁晓明 1于利双 1李春岩 1李媛媛1
作者信息
- 1. 050000 石家庄,河北医科大学第二医院神经内科
- 折叠
摘要
目的 探讨IKKβ抑制剂对肌萎缩侧索硬化症(ALS)运动神经元的保护性作用.方法 首先在ALS模型小鼠腰髓的运动神经元中鉴定IKK β的表达情况;然后利用稳定表达SOD1G93A的NSC34细胞系,给予IKKβ抑制剂(TPCA-1)后,观察抑制剂对神经元的影响,包括蛋白印迹方法观察细胞增殖、凋亡及炎症相关指标的变化.结果 ALS模型小鼠腰髓运动神经元中IKKβ的表达较同窝对照小鼠明显增多;给予IKKβ抑制剂后,与细胞增殖有关的指标磷酸化细胞外信号调节激酶p-Erk较对照组有所增加;凋亡蛋白活化的Caspase-3明显减少;核转录因子(NF-κB)信号通路相关指标IKKβ、PP65明显减少;炎症因子诱导型一氧化氮合酶(iNOS)表达有所减少,与对照组相比,差异有统计学意义.结论 IKKβ抑制剂(TPCA-1)促进NSC34-SOD1G93A细胞的增殖、抑制凋亡及促炎细胞因子的产生,对神经元有保护性作用.
Abstract
Objective To investigate the protective effect of IKK β inhibitor on motor neurons in amyotrophic lateral sclerosis(ALS).Methods Firstly,the expression of IKK β in motor neurons of lumbar spinal cord of ALS model mice was identified.Then,NSC34 cell line stably expressing SOD1G93A was administered with IKK β inhibitor(TPCA-1),and Western blot method was used to compare the effects of IKK β inhibition on neurons,including cell proliferation,apoptosis and inflammation.Results The expression of IKK β in lumbar spinal motor neurons of ALS model mice was significantly increased compared with that of control mice.After administration of IKK β inhibitors,the cell proliferation related markers p-Erk was increased compared with the control group.The apoptotic protein C-Caspase-3 decreased significantly.The expression of NF-κB signaling pathway related index IKK β、PP65 significantly decreased.The levels of inflammatory factors iNOS was decreased,which showed significant differences compared with the control group.Conclusion IKK β inhibitor(TPCA-1)promoted the proliferation of NSC34-SOD1 G93A cells,inhibited apoptosis and production of pro-inflammatory cytokines,and had protective effects on neurons.
关键词
肌萎缩侧索硬化/IκB激酶β/神经元/细胞增殖/炎症因子Key words
Amyotrophic lateral sclerosis/Inhibitory kappa B kinase beta/Neuron/Cell proliferation/Inflammatory factor引用本文复制引用
出版年
2025
NETL
NSTL
万方数据