郑州大学学报（医学版）2025，Vol.60Issue(2)：249-256,8.DOI:10.13705/j.issn.1671-6825.2024.08.054
刺芒柄花素对变应性鼻炎小鼠鼻黏膜组织铁死亡和NLRP3炎症小体活化的影响
Effect of formononetin on ferroptosis and NLRP3 inflammasome activation in nasal mucosa tissue of mice with allergic rhinitis
摘要
Abstract
Aim:To explore the effects of formononetin on ferroptosis and nucleotide-binding domain leucine-rich re-peat and pyrin domain-containing receptor 3(NLRP3)inflammasome activation in mice with allergic rhinitis and its mecha-nism.Methods:Sixty male Balb/c mice were randomly allocated into control group,model group,low dose formononetin group,high dose formononetin group,and formononetin+EX527 group,with 12 in each group.Except for the mice in control group,the mice in other groups were exposed to ovalbumin(OVA)to construct the allergic rhinitis model.The nasal symp-toms(scratching nose and sneezing)were observed by behavioral observation.The serum levels of OVA specific IgE(OVA-sIgE)and histamine were determined by ELISA.The morphological changes of nasal mucosa and the numbers of eosino-phils,goblet cells and mast cells were determined.The levels of reactive oxygen species(ROS),glutathione(GSH),malond-ialdehyde(MD A),and Fe2+in nasal mucosa tissue were determined by kits.The mRNA expressions of glutathione peroxi-dase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by qRT-PCR.The protein expressions of silencing information regulator 1(SIRT1),NLRP3,apoptosis associated speckled-like protein(ASC),Cleaved Caspase-1,Cleaved interleukin-1 β(IL-1 β),IL-18,GPX4,and SLC7A11 were detected by Western blot.The acetylation level of NLRP3 was determined by immunoprecipitation.Results:Compared with the model group,the frequency of scratching nasal and sneezing in low and high dose formononetin groups were reduced,serum levels of OVA-sIgE and histamine were decreased,the nasal mucosa damage was alleviated,and the numbers of eosinophils,mast cells,and goblet cells were reduced(P＜0.05);the levels of ROS,MDA,and Fe2+were decreased,while GSH level and GPX4 and SLC7A11 mRNA and protein ex-pressions levels were increased in low and high dose formononetin groups(P＜0.05);the protein expressions levels of SIRT1,NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,and IL-18 as well as the acetylation level of NLRP3 were de-creased(P＜0.05).SIRT1 inhibitor EX527 attenuated the inhibitory effects of formononetin on ferroptosis and NLRP3 in-flammasome activation in nasal mucosa of mice with allergic rhinitis.Conclusion:Formononetin can inhibit the ferroptosis and NLRP3 inflammasome activation in nasal mucosa of mice with allergic rhinitis via regulating SIRT1 protein.关键词
刺芒柄花素/变应性鼻炎/沉默信息调节因子1/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3/铁死亡/小鼠Key words
formononetin/allergic rhinitis/silencing information regulator 1/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3/ferroptosis/mouse分类
医药卫生引用本文复制引用
丁虹,王雪可,芦晓帆,许誉琦..刺芒柄花素对变应性鼻炎小鼠鼻黏膜组织铁死亡和NLRP3炎症小体活化的影响[J].郑州大学学报（医学版）,2025,60(2):249-256,8.基金项目
河南省中医药科学研究专项(2022ZY1057) （2022ZY1057）
河南省重点研发与推广专项(科技攻关)项目(242102311066) （科技攻关）
