NF-κB介导的神经炎症在脑膜癌病中的研究  

Study on the mechanism of NF-kB mediated neuroinflammation in leptomeningeal metastasis

作　　者：李媛媛[1] 李忠尧[1] 毕悦 刘亚坤[1] Li Yuanyuan Li Zhongyao;Bi Yue;Liu Yakun(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

出　　处：《脑与神经疾病杂志》2020年第1期28-32,共5页Journal of Brain and Nervous Diseases

基　　金：2018年河北省省级科技计划自等经费项目(182777134)

摘　　要：目的观察敲减肺腺癌细胞或条件性敲除小胶质细胞中的IκB激酶β(IKKβ)后,对脑膜癌病(LM)的影响。方法利用以HIV-1(人类免疫缺陷I型病毒)为基础的慢病毒感染的方法,敲减肺腺癌细胞中的IKKβ,通过嘌呤霉素筛选及流式细胞仪分选技术,分别建立敲减IKKβ组及对照组的稳转细胞株,通过qPCR方法比较敲减IKKβ后对肿瘤细胞的影响,以及观察条件性敲除小胶质细胞中的IKKβ后,对荷瘤小鼠生存期的影响。结果将肺腺癌细胞中的IKKβ敲减后,与对照组相比,NF-κB介导的部分炎症因子的表达水平明显降低,包括IL-6、IL-1β、TNF-α;与对照组小鼠相比,条件性敲除小胶质细胞中的IKKβ后,荷瘤小鼠的生存期明显延长。结论敲减肺腺癌细胞中的IKKβ后,可以明显减轻NF-κB介导的炎症反应,敲除小胶质细胞中的IKKβ后,可以明显延长荷瘤小鼠的寿命。Objective To observe the effect of knockdown IKKβ in lung adenocarcinoma cells or conditional knockout of IKKβ in microglia on leptomeningeal metastasis(LM). Methods After infected by Lentivirus, stable cell lines were established in the knockdown IKKβ group and the control group by puromycin screening and flow cytometry, respectively. The effect of knockdown IKKβ on tumor cells was compared by qPCR. The survival time of tumor-bearing mice was observed in conditioned microglia knockout IKKβ mice and the littermate control mice. Results When IKKβ was knocked down in lung adenocarcinoma cells, levels of NF-κB-mediated inflammatory factors, including IL-6, IL-1β and TNF-α, were significantly lower than those in the control group. Compared with control mice, tumor-bearing mice survived significantly longer after conditioned knockout of IKKβ in microglia cells. Conclusion Knockdown of IKKβ in lung adenocarcinoma cells significantly reduced NF-κBmediated inflammatory response, and knockdown of IKKβ in microglia significantly extended the life span of tumorbearing mice.

关 键 词：IκB激酶β 肺腺癌 神经炎症 脑膜转移 

分 类 号：R739.4[医药卫生—肿瘤]