文章摘要
须怀沙,王易欣,陈旭锋,蒋 雷,王 军,张久平.甲基苯丙胺引起BV2小胶质细胞炎性反应:基于Toll样受体⁃Peli1信号通路的研究[J].南京医科大学学报,2021,(3):324~330
甲基苯丙胺引起BV2小胶质细胞炎性反应:基于Toll样受体⁃Peli1信号通路的研究
Methamphetamine induced neuroinflammation in microglial BV2 cells based on the roles of Toll like receptors⁃Peli1 pathway
投稿时间:2020-09-09  
DOI:10.7655/NYDXBNS20210303
中文关键词: 甲基苯丙胺  Toll样受体家族  Peli1  神经炎性反应  BV2细胞
英文关键词: methamphetamine  Toll like receptors  Peli1  neuroinflammation  BV2 cell
基金项目:国家自然科学基金(81673213);江苏省自然科学基金(BK20191349)
作者单位
须怀沙 南京鼓楼医院医学心理科江苏 南京 210008 
王易欣 南京医科大学公共卫生学院卫生毒理系江苏 南京 211166 
陈旭锋 南京医科大学第一附属医院急诊科江苏 南京 210029 
蒋 雷 南京医科大学第一附属医院急诊科江苏 南京 210029 
王 军 南京医科大学公共卫生学院卫生毒理系江苏 南京 211166 
张久平 南京医科大学附属脑科医院儿童心理卫生研究中心江苏 南京 210029 
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中文摘要:
      目的:探讨Toll样受体(Toll like receptor,TLR)?E3泛素连接酶Pellino 1(Peli1)介导的炎性通路在甲基苯丙胺(methamphetamine,Meth)引起BV2小胶质细胞炎性反应中的作用。方法:利用Western blot观察Meth作用后Toll样家族中多种TLR的表达及其下游接头蛋白髓样分化因子(myeloid differentiation factor 88,MyD88)、β干扰素TIR结构域衔接蛋白(TIR?domain?containing adaptor inducing interferon?β,TRIF)水平的改变,同时观察上述接头蛋白下游Peli1蛋白的表达,利用ELISA、实时定量PCR(real time?PCR)及Western blot观察Peli1调节的下游炎性因子及信号通路的改变。结果:Meth作用于BV2细胞后,TLR3、TLR4、TLR7、TLR8、TLR11在特定时间内表达明显上调,同时下游MyD88及TRIF蛋白表达显著增加,其中TRIF具有浓度依赖效应。Meth作用后亦可引起泛素化蛋白Peli1的表达,而利用RNA干扰的方法将Peli1下调后,炎性因子诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、肿瘤坏死因子(tumor necrosis factor,TNF)?α、白细胞介素(interleukin? 6,IL)?6表达下降,核因子(nuclear factor,NF)?κB的激活明显缓解。结论:TLR介导的炎性信号在Meth引起BV2细胞炎性反应过程中发挥重要作用。因此,基于TLRs?Peli1靶信号轴的干预可能为Meth神经毒性的干预提供靶点,具有潜在的应用意义。
英文摘要:
      Objective:This study aims to investigate the roles of Toll like receptor(TLR)?Pellino 1(Peli1) axis in methamphetamine(Meth)?mediated microglial inflammation and pathway in BV2 cells. Methods:Western blot was used to observe the expression of Toll like receptors(TLR),the downstream adaptor proteins of myeloid differentiation factor 88(MyD88)and TIR?domain?containing adaptor inducing interferon?β(TRIF). In parallel,the expression of Peli1 protein was detected by Western blot. The downstream inflammatory factors and signal pathway regulated by Peli1 were observed by ELISA,real?time PCR and Western blot. Results:The expression of TLR3,TLR4,TLR7,TLR8 and TLR11 was significantly up?regulated after Meth treatment in BV2 cells. Meanwhile,the expression of MyD88 and TRIF was significantly increased,and TRIF level exhibited a concentration?dependent effect. Meanwhile,Meth obviously induced the expression of ubiquitin protein Peli1. Noteworthily,after Peli1 was down?regulated by RNA interference,the expression of inflammatory factors including inducible nitric oxide synthase(iNOS),tumor necrosis factor(TNF)?α and interleukin(IL)?6 were dramatically decreased,accompanied by the significant attenuation of nuclear factor(NF)?κB activation. Conclusion:The TLRs?mediated inflammatory signal plays an important role in the process of microglial inflammatory response induced by Meth. Therefore,the TLRs?Peli1 signal axis may be a promising target for the intervention of Meth neurotoxicity,which displays significant application.
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