基于TLR4/NF-κB通路探讨泊马度胺对帕金森病小鼠的作用机制  

Explore the mechanism of action of pomalidomide in mice with Parkinson’s disease based on the TLR4/NF-κB pathway

作　　者：王梦涵[1] 卢宏[1] WANG Menghan;LU Hong(The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院,河南郑州450052

出　　处：《中国实用神经疾病杂志》2023年第5期529-533,共5页Chinese Journal of Practical Nervous Diseases

摘　　要：目的探讨泊马度胺(Pom)通过TLR4/NF-κB通路对帕金森病(PD)小鼠模型的作用机制。方法雄性C57BL6小鼠随机分为正常对照组(Control组)、MPTP组、泊马度胺组(Pom组)。MPTP组、泊马度胺组模型均腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)构建模型,对各组模型小鼠进行行为学评价。免疫荧光染色测定脑内活化的小胶质细胞,Western blotting检测炎症因子、TLR4/NF-κB通路蛋白等的表达。结果与MPTP组小鼠相对比,Pom组小鼠神经功能明显改善,小胶质细胞活化的数量明显减少,且炎症因子的表达显著降低,差异有统计学的意义(P<0.05)。结论泊马度胺可以通过TLR4/NF-κB通路抑制帕金森病小鼠小胶质细胞的增生,减少炎症因子的表达,有效改善帕金森病小鼠的神经功能。Objective To investigate the mechanism of action of pomalidomide(Pom)on Parkinson’s disease(PD)mouse model through TLR4/NF-κB pathway.Method Male C57BL6 mice were randomly divided into a normal control group(control group),MPTP group,and Pomalidomide group(Pom group).The models in the MPTP and Pomalidomide groups were constructed by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetra⁃hydropyridine(MPTP),and behavioral evaluation was performed for each group of model mice.The expression of inflammatory factors and TLR4/NF-κB pathway proteins were measured by immunofluorescence staining of activat⁃ed microglia in the brain and western blotting.Results Compared with the mice in the MPTP group,the mice in the Pom group showed significantly improved neurological function,the number of activated microglia was signifi⁃cantly decreased,the expression of inflammatory factors was significantly reduced,and the differences were statisti⁃cally significant(P<0.05).Conclusion Pomalidomide can inhibit the proliferation of microglia in Parkinson’s disease mice through TLR4/NF-κB pathway,decrease the expression of inflammatory factors,and effectively im⁃prove the neurological function of Parkinson’s mice.

关 键 词：帕金森病 泊马度胺 TLR4/NF-κB信号通路 神经炎症 

分 类 号：R742.5[医药卫生—神经病学与精神病学]