Nurr1通过抑制小胶质细胞NF-κB发挥抗炎作用  

Nurr1 attenuates microglia inflammation by inhibiting NF-κB

作　　者：王伟[1] 侯晓霖[1] 陈秋元 潘晓玥 彭涛[2] 王俊燕 李云鸿[2] 王银[2] WANG Wei;HOU Xiaolin;CHEN Qiuyuan;PAN Xiaoyue;PENG Tao;WANG Junyan;LI Yunhong;WANG Yin(General Hospital of Ningxia Medical University,Yinchuan 750004,China;School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院,宁夏银川750004 [2]宁夏医科大学基础医学院,宁夏银川750004

出　　处：《宁夏医学杂志》2024年第4期281-284,F0002,共5页Ningxia Medical Journal

基　　金：国家自然科学基金项目(82060223);宁夏自然科学基金项目(2022AAC03607,2021AAC03372);宁夏重点研发基金项目(2021BEG03097)。

摘　　要：目的探索在细菌脂多糖(LPS)诱导的小鼠小胶质细胞(BV2细胞株)炎症反应中,核受体相关蛋白1(Nurr1)是否通过抑制NF-κB的表达及核转位发挥抗炎作用。方法培养小鼠BV2小胶质细胞株,将细胞分为Ctrl组、LPS组、C-DIM12(Nurrl特异性激动剂)组、siRNA干扰组、LPS+C-DIM12组。利用CCK-8检测LPS和C-DIM12的最适作用浓度,用Western blot观察NF-κB和Nurr1的表达变化,用酶联免疫吸附法(ELISA)检测培养液中炎症因子IL-6、IL-1β和TNF-α的水平,用免疫荧光观察siRNA干扰或C-DIM12激活Nurr1表达活性后,NF-κB及p-IκB在BV2细胞中的表达水平。结果LPS刺激BV2细胞后,NF-κB表达提高,炎症因子IL-1、IL-6、TNF-α释放量增加(P<0.05)。C-DIM12激活Nurr1后,免疫荧光染色技术和Western blot实验结果都显示NF-κB的表达显著下降,而小干扰RNA(siNurr1)沉默Nurr1表达后,NF-κB表达增加。在LPS激活的小胶质细胞中,NF-κB二聚体分子的结合分子p-IκB的磷酸化蛋白水平相对于对照组显著升高,而C-DIM12激活Nurr1后,p-IκB水平显著下降。结论Nurr1可以通过抑制小胶质细胞NF-κB表达水平并阻止NF-κB核位移发挥抗炎作用。Nurr1可能是一个新的潜在的治疗中枢神经系统炎症相关疾病的靶点。Objective To explore whether Nurr1 inhibits NF-κB expression and nuclear translocation in BV2 microglia inflammatory response induced by LPS to play an anti-inflammatory role.Methods Mouse BV2 microglia cells were cultured and divided into Ctrl group,LPS group,C-DIM12 group(Nurr1 specific agonist),siRNA interference group and LPS+C-DIM12 group.CCK-8 was used to detect the optimal concentration of LPS and C-DIM12,and the expression changes of NF-κB and Nurr1 were measured by Western blot,and the inflammatory factors IL-6,IL-1βand TNF-αlevels were detected by ELISA.After the expression activity of Nurr1 was disrupted by siRNA or activated by C-DIM12,the expression levels of NF-κB and p-IκB in BV2 cells were investigated.Results After the BV2 cells were stimulated by LPS,the expression of NF-κB increased and the release of inflammatory factors IL-1,IL-6,TNF-αalso increased(P<0.05).After Nurr1 was activated by C-DIM12,the expression of NF-κB decreased significantly.However,after small interfering RNA(siNurr1)silenced the expression of Nurr1,the expression of NF-κB increased.In LPS-activated microglia,the level of phosphorylated protein I-κB,which was NF-κB dimer molecule binding molecule,was significantly higher than that in the control group.After Nurr1 was activated by C-DIM12,pI-κB level decreased significantly.Conclusion Nurr1 can inhibit the expression of NF-κB,reverse NF-κB nuclear translocation and protect the CNS from inflammation.Nurr1 may be a new and potential target for the treatment of inflammation related CNS diseases.

关 键 词：NURR1 NF-ΚB 神经炎症 小胶质细胞 p-IκB 

分 类 号：R739.41[医药卫生—肿瘤]