南方医科大学学报2026，Vol.46Issue(5)：994-1005,12.DOI:10.12122/j.issn.1673-4254.2026.05.03
KLF10通过下调NF-κB/NLRP3通路改善大鼠焦虑性抑郁行为及神经炎症
KLF10 overexpression alleviates neuroinflammation and anxiety-depressive disorder in rats by downregulating the NF-κB/NLRP3 pathway
摘要
Abstract
Objective To elucidate the neuroimmune regulatory mechanism of the circadian rhythm gene KLF10 as a biomarker for anxiety depressive disorder(ADD).Methods The differentially expressed circadian rhythm genes were screened using human peripheral blood gene chip data from the GEO database(including 64 healthy individuals,62 patients with major depressive disorder[MDD],and 59 with ADD)in conjunction with the MSigDB database.Weighted gene co-expression network analysis and machine learning models were employed to identify the core genes,followed by KEGG pathway enrichment analysis and evaluation of their diagnostic efficacy using ROC curves.In a male SD rat model of ADD induced by chronic restraint and corticosterone stress,the changes in depressive-like behaviors,hippocampal and amygdala pathologies,levels of inflammatory and pro-inflammatory cytokines,co-localization of KLF10 and p-p65 expression,and expression levels of NF-κB/NLRP3 pathway molecules were examined following stereotactic AAV virus injection into the lateral ventricle for KLF10 overexpression.Results Compared with healthy individuals,the depressive patients showed differential expressions of 9 circadian rhythm genes.Compared with the MDD patients,the patients with ADD had significantly higher immune infiltration scores with upregulated NOD-like receptor and NF-κB signaling pathways.The specific biomarker KLF10 demonstrated a diagnostic efficacy of 0.885.In the rat models of AOD,KLF10 overexpression significantly ameliorated depression-and anxiety-like behaviors,restored the balance between the pro-and anti-inflammatory cytokines,and improved hippocampal and amygdala pathologies.KLF10 overexpression also markedly upregulated NFKBIA mRNA,downregulated NLRP3 and RELA mRNAs,and reduced protein expressions of p-IκB-α,p-p65,and NLRP3 in the brain tissues of the rats.Conclusion KLF10 overexpression ameliorates ADD behaviors in rats by inhibiting hippocampal-amygdala inflammation via downregulating the NF-κB/NLRP3 pathway,suggesting the potential of KLF10 as a diagnostic biomarker and therapeutic target for AOD.关键词
焦虑性抑郁/神经炎症/NF-κB/NLRP3通路/昼夜节律基因Key words
anxiety-depressive disorder/neuro-inflammation/NF-κB/NLRP3 pathway/circadian rhythm genes引用本文复制引用
刘安澜,过伟峰,李建香,张天鸽,徐丹..KLF10通过下调NF-κB/NLRP3通路改善大鼠焦虑性抑郁行为及神经炎症[J].南方医科大学学报,2026,46(5):994-1005,12.基金项目
国家自然科学基金(82074309) （82074309）
江苏省教育厅江苏省研究生科研创新计划项目(KYCX23_2123) （KYCX23_2123）
苏州市科技局基础应用研究(SKYD2023236)Supported by National Natural Science Foundation of China(82074309). （SKYD2023236）
