IKKβ抑制剂对肌萎缩侧索硬化症的保护性作用  

Protective effects of IKKβinhibitor on amyotrophic lateral sclerosis

作　　者：刘亚坤[1] 温迪[1] 祁晓明 于利双 李春岩[1] 李媛媛[1] Liu Yakun;Wen Di;Qi Xiaoming;Yu Lishuang;Li Chunyan;Li Yuanyuan(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《脑与神经疾病杂志》2025年第2期126-129,共4页Journal of Brain and Nervous Diseases

基　　金：河北省自然科学基金资助项目(H2024206009)。

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IKKβ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。Objective To investigate the protective effect of IKKβinhibitor on motor neurons in amyotrophic lateral sclerosis(ALS).Methods Firstly,the expression of IKKβin motor neurons of lumbar spinal cord of ALS model mice was identified.Then,NSC34 cell line stably expressing SOD1~(G93A)was administered with IKKβinhibitor(TPCA-1),and Western blot method was used to compare the effects of IKKβinhibition on neurons,including cell proliferation,apoptosis and inflammation.Results The expression of IKKβin lumbar spinal motor neurons of ALS model mice was significantly increased compared with that of control mice.After administration of IKKβinhibitors,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 IKKβ、PP65 significantly decreased.The levels of inflammatory factors iNOS was decreased,which showed significant differences compared with the control group.Conclusion IKKβinhibitor(TPCA-1)promoted the proliferation of NSC34-SOD1 G93A cells,inhibited apoptosis and production of proinflammatory 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 

分 类 号：R741[医药卫生—神经病学与精神病学]