Nurr1对细菌脂多糖诱导的小胶质细胞凋亡、自噬和铁死亡的抑制作用  

Inhibitory Effect of Nurr1 on Apoptosis,Autophagy and Ferroptosis of LPS-induced Microglia

作　　者：彭涛[1] 陈秋元 王俊燕 何学仙 李云鸿[1] 王银[1] 侯晓霖[2] PENG Tao;CHEN Qiuyuan;WANG Junyan;HE Xuexian;LI Yunhong;WANG Yin;HOU Xiaolin(Department of Physiology and Neurobiology,School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China;General Hospital of Ningxia Medical University,First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院生理学与神经生物学系,银川750004 [2]宁夏医科大学总医院,宁夏医科大学第一临床医学院,银川750004

出　　处：《宁夏医科大学学报》2024年第11期1091-1095,1115,共6页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2021AAC03372,2023AAC02037,2023AAC03162);宁夏重点研发计划项目(2021BEG03097)。

摘　　要：目的研究核受体相关蛋白1(Nurr1)对细菌脂多糖(LPS)诱导的BV2小胶质细胞活性即细胞凋亡、自噬及铁死亡的作用,从而探究Nurr1通过调节小胶质细胞活性发挥神经保护作用的机制。方法培养小鼠BV2小胶质细胞株,将细胞分为Ctrl组、LPS组、C-DIM12组(Nurr1特异性激动剂)、LPS+C-DIM12组。利用Western blot观察Toll样受体4(TLR4)和Caspase-3的表达变化,流式细胞术检测细胞凋亡情况。检测利用Nurr1的特异性激动剂C-DIM12激活Nurr1的表达活性后,自噬蛋白LC3Ⅱ和铁死亡标志物谷胱甘肽过氧化物酶4(GPX4)的表达变化及脂质过氧化物产物丙二醛(MAD)的水平。结果LPS刺激BV2细胞后,TLR4和Caspase-3的表达升高(P均<0.05)。C-DIM12激活Nurr1后,TLR4和Caspase-3的表达下降。流式细胞实验结果也显示,Nurr1的激活抑制了细胞凋亡。C-DIM12激活Nurr1后,自噬蛋白LC3Ⅱ的表达相对于LPS组下降,铁死亡蛋白GPX4升高,而MDA显著下降(P均<0.05)。结论Nurr1可通过抑制LPS诱导的小胶质细胞的凋亡、自噬和铁死亡发挥神经保护作用。Nurr1可能是治疗中枢神经系统疾病的潜在靶点。Objective To investigate the effect of nuclear receptor-related protein 1(Nurr1)on the viability including apoptosis,autophagy and ferroptosis of BV2 microglial cells induced by bacterial lipopolysaccharide(LPS),so as to explore the neuroprotective effect of Nurr1.Methods BV2 cells were cultured and divided into Ctrl group,LPS group,C-DIM12 group(Nurr1 specific agonist),LPS+C-DIM12 group.Western blot was used to observe the expression of TLR4 and Caspase3,and flow cytometry was used to detect apoptosis.The expression changes of autophagy protein LC3Ⅱand ferroptosis marker glutathione peroxidase4(GPX4)and MDA were detected after activating the expression activity of Nurr1 with the specific agonist C-DIM12 of Nurr1.Results After LPS activated BV2 cells,the expression of TLR4 and Caspase3 increased significantly(P>0.05).After activating Nurr1 by C-DIM12,the expression of TLR4 and Caspase3 decreased significantly(P>0.05).Flow cytometry also showed that the activation of Nurr1 inhibited cell apoptosis.After C-DIM12 activated Nurr1,the expression of autophagic protein LC3Ⅱwas obviously decreased compared with LPS group,and the expression of ferroptosis protein GPX4 was remarkably increased,but MDA level decreased.Conclusion Nurr1 may play a neuroprotective role by inhibiting LPS-induced apoptosis,autophagy and ferroptosis of microglia.Nurr1 may be a potential target for the treatment of central nervous system diseases.

关 键 词：核受体相关蛋白1 神经保护 小胶质细胞 细胞凋亡 自噬 铁死亡 

分 类 号：R739.41[医药卫生—肿瘤]