中国病理生理杂志2026，Vol.42Issue(3)：487-496,10.DOI:10.3969/j.issn.1000-4718.2026.03.008
小胶质细胞P2Y6受体通过NLRP3-caspase-1-IL-1β通路介导福尔马林诱导的小鼠急性炎性疼痛
Microglial P2Y6 receptor mediates formalin-induced acute inflammato-ry pain in mice via NLRP3-caspase-1-IL-1β signaling pathway
摘要
Abstract
AIM:To investigate the role of the microglial P2Y6 receptor in formalin-induced acute inflamma-tory pain and its underlying molecular mechanisms in mice.METHODS:An acute inflammatory pain model was estab-lished by plantar injection of formalin in C57BL/6 mice.The animals were randomly divided into the following groups:the sham group,pain model group,P2Y6 receptor agonist uridine diphosphate(UDP)group,and P2Y6 receptor inhibitor(MRS2578)group,with 15 mice in each group.Additionally,P2Y6-/-and P2Y6+/+C57BL/6 mice were used,with 15 mice in each group.Transgenic C57BL/6 mice with P2Y6-/-:CX3CR1GFP/+and P2Y6+/+:CX3CR1GFP/+genotypes were con-structed,with 9 mice in each group.BV2 microglia were divided into 4 groups:control,UDP,UDP+MRS2578,and MRS2578.Pain-related behaviours were analysed,and two-photon in vivo imaging was employed to dynamically observe microglial branch motility in the spinal dorsal horn.Immunofluorescence staining and Western blot were used to assess mi-croglial density,the expression of the inflammatory cytokine interleukin-1β(IL-1β),and changes in key molecules of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)-caspase-1 signaling pathway.RESULTS:Pharmacological activation of the P2Y6 receptor exacerbated formalin-induced pain behaviours,whereas its inhibition or genetic deletion significantly alleviated pain in mice(P<0.05).Two-photon imaging revealed that P2Y6 knockout effec-tively suppressed the enhanced microglial process dynamics in the spinal cord induced by formalin(P<0.05).At 24 hours post-pain induction,P2Y6 knockout significantly reduced the density of accumulated microglia in the spinal dorsal horn(P<0.01).Both in vivo and in vitro experiments confirmed that P2Y6 gene deletion or pharmacological inhibition significant-ly suppressed NLRP3 inflammasome activity and caspase-1 activation,concurrently reducing the release of IL-1β from mi-croglia(P<0.05).CONCLUSION:In a mouse model of acute inflammatory pain,the P2Y6 receptor regulates the dy-namic motility of microglial branches and promotes their subsequent aggregation in the spinal dorsal horn.Moreover,it ac-tivates the NLRP3-caspase-1-IL-1β signaling pathway,thereby contributing to the development and maintenance of forma-lin-induced inflammatory pain during the acute phase.关键词
P2Y6受体/急性炎性疼痛/福尔马林/小胶质细胞/NLRP3-caspase-1-IL-1β信号通路Key words
P2Y6 receptor/acute inflammatory pain/formalin/microglia/NLRP3/caspase-1/IL-1β signaling pathway分类
医药卫生引用本文复制引用
陈洪懿,朱烨杰,余嘉慧,焦子墨,沈晓华,朱佳..小胶质细胞P2Y6受体通过NLRP3-caspase-1-IL-1β通路介导福尔马林诱导的小鼠急性炎性疼痛[J].中国病理生理杂志,2026,42(3):487-496,10.基金项目
嘉兴市科技计划项目(No.2025CGZ028) （No.2025CGZ028）
浙江省医药卫生科技计划项目(No.2025KY1628) （No.2025KY1628）
嘉兴大学省级大学生创新训练计划项目(No.S202510354059) （No.S202510354059）
