南方医科大学学报2025，Vol.45Issue(5)：901-910,10.DOI:10.12122/j.issn.1673-4254.2025.05.02
精胺抑制巨噬细胞中GBP5介导的NLRP3炎性小体活化减轻感染肠道病毒71型的新生小鼠脏器损伤
Spermine suppresses GBP5-mediated NLRP3 inflammasome activation in macrophages to relieve vital organ injuries in neonatal mice with enterovirus 71 infection
摘要
Abstract
Objective To observe the therapeutic effect of spermine in neonatal mouse models of severe hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71)infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway.Methods Neonatal BALB/c mice(3-5 days old)were divided into control group,EV71 infection group and Spermine treatment group.The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension(1×10⁶ TCID50 of EV71),followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine.GBP5,NLRP3,CXCL10,and TNFSF10 expressions in heart,liver,lung and kidney tissues of the mice were detected using Western blotting and qPCR,and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry.In cultured THP-1 and RAW264.7 cells,the effects of EV71 infection,GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5,NLRP3,CXCL10,and TNFSF10 mRNA expressions were investigated using qPCR.Results In the neonatal mice,EV71 infection resulted in multiple organ damage,macrophage infiltration and activation of the GBP5/NLRP3 pathway,and spermine treatment significantly improved tissue injuries,reduced macrophage infiltration,and down-regulated the expressions of GBP5,NLRP3 and the inflammatory factors in the infected mice.In THP-1 and RAW264.7 cells,EV71 infection caused significant upregulation of GBP5,NLRP3,CXCL10,and TNFSF10 expressions,which were obviously lowered by spermine treatment.In THP-1 cells,treatment with eflornithine significantly suppressed the reduction of GBP5,NLRP3,CXCL10,and TNFSF10 expressions induced by GBP5 siRNA transfection.Conclusion Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation,suggesting a new strategy for treatment of severe HFMD.关键词
重症手足口病/肠道病毒71型/NLRP3/GBP5/巨噬细胞/精胺Key words
severe hand-foot-mouth disease/enterovirus 71/NLRP3/GBP5/macrophages/spermine引用本文复制引用
田芷华,杨青青,陈欣,张方方,钟柏茂,曹虹..精胺抑制巨噬细胞中GBP5介导的NLRP3炎性小体活化减轻感染肠道病毒71型的新生小鼠脏器损伤[J].南方医科大学学报,2025,45(5):901-910,10.基金项目
广东省基础与应用基础研究项目——区域联合基金——地区培养项目(2021B1515140002) （2021B1515140002）
东莞市科技计划(20231800940142) （20231800940142）
