中国中医药信息杂志2025，Vol.32Issue(5)：90-97,8.DOI:10.19879/j.cnki.1005-5304.202409338
基于WDFY1/TLR4/NF-κB信号通路探讨开心散对APP/PS1小鼠神经炎症的影响
Effects of Kanxin Powder on Neuroinflammation in APP/PS1 Mice Based on WDFY1/TLR4/NF-κB Signaling Pathway
摘要
Abstract
Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.关键词
阿尔茨海默病/开心散/APP/PS1小鼠/WDFY1/TLR4/NF-κB信号通路/神经炎症Key words
Alzheimer disease/Kaixin Powder/APP/PS1 mice/WDFY1/TLR4/NF-κB signaling pathway/neuroinflammation分类
医药卫生引用本文复制引用
杨雅丽,张力,闵冬雨,刘勇明,袁常斌,鞠业涛,梁元钰,程美佳,何晓明,于畅洋..基于WDFY1/TLR4/NF-κB信号通路探讨开心散对APP/PS1小鼠神经炎症的影响[J].中国中医药信息杂志,2025,32(5):90-97,8.基金项目
国家自然科学基金(82174114) （82174114）
沈阳市科学技术计划公共卫生研发专项-医工结合协同创新研究项目(22-321-32-14) （22-321-32-14）
辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金(zyzx2006) （zyzx2006）
