中医药信息2025，Vol.42Issue(5)：21-28,44,9.DOI:10.19656/j.cnki.1002-2406.20250504
山柰酚调控TLR4/NF-κB/NLRP3通路介导的细胞焦亡途径对变应性鼻炎大鼠的影响
Effect of Kaempferol on Allergic Rhinitis Rats via Regulating the TLR4/NF-κB/NLRP3 Pathway Mediated Cell Apoptosis Pathway
摘要
Abstract
Objective:To investigate the mechanism of kaempferol(KPF)in regulating the TLR4/NF-κB/NLRP3 pathway-mediated pyroptosis in allergic rhinitis(AR)rats.Methods:Ninety SD rats were randomly divided into the control group,KPF-H+TLR4 agonist group,AR group,KPF low-dose group(KPF-L group),KPF medium-dose group(KPF-M group),and KPF high-dose group(KPF-H group),with 15 rats in each group.Except for the Control group,the other groups were intraperitoneally injected with ovalbumin(OVA)-aluminum hydroxide suspension every other day for 7 times;14 days later,2%OVA was instilled nasally twice daily for 7 days to establish the AR model.After successful modeling,the KPF-L,KPF-M,and KPF-H groups were given 10,25,and 50 mg/kg KPF by gavage,respectively;the KPF-H+TLR4 agonist group was intravenously injected with lipopolysaccharide(LPS)3 mg/kg via the tail vein while receiving 50 mg/kg KPF by gavage;the Control group and AR group were given an equivalent volume of saline by gavage;all treatments were administered once daily for 10 consecutive days.The following evaluations were performed:assessment of behavioral symptom scores in each group of rats;observation of histopathological changes in nasal mucosa tissues by hematoxylin-eosin(HE)staining;measurement of serum IL-1β,IL-18,IL-4,and IFN-γ levels by ELISA;detection of pyroptosis rate by propidium iodide(PI)staining;Western blot analysis of pyroptosis-related proteins(Caspase-1 p20/Caspase-1 p45,GSDMD-N/GSDMD,IL-18,IL-1β)and TLR4/NF-κB/NLRP3 pathway proteins(TLR4,p-NF-κB/NF-κB,NLRP3)in nasal mucosa tissues;immunohistochemical detection of TLR4,p-NF-κB,and NLRP3 protein expression in nasal mucosa tissues.Results:Compared with the Control group,the AR group showed significantly increased behavioral symptom scores,IL-1β,IL-18,and IL-4 levels,pyroptosis rate,expression of pyroptosis-related proteins,and expression of TLR4,p-NF-κB,and NLRP3 proteins(P<0.05),while IFN-γ levels were significantly decreased(P<0.05).The nasal mucosa exhibited disordered epithelial cell arrangement,inflammatory cell infiltration,necrotic cell shedding,mucosal congestion,and significant pathological damage.Compared with the AR group,all KPF treatment groups showed significantly decreased behavioral symptom scores,IL-1β,IL-18,and IL-4 levels,pyroptosis rate,expression of pyroptosis-related proteins,and expression of TLR4,p-NF-κB,and NLRP3 proteins(P<0.05),while IFN-γ levels were significantly increased(P<0.05),and pathological damage in the nasal mucosa was significantly alleviated.Compared with the KPF-H group,the KPF-H+TLR4 agonist group showed significantly increased behavioral symptom scores,IL-1β,IL-18,and IL-4 levels,pyroptosis rate,expression of pyroptosis-related proteins,and expression of TLR4,p-NF-κB,and NLRP3 proteins(P<0.05),while IFN-γ levels were significantly decreased(P<0.05),and pathological damage in the nasal mucosa was aggravated.Conclusion:KPF can inhibit TLR4/NF-κB/NLRP3 signaling pathway-mediated pyroptosis,reduce inflammatory responses,and improve nasal mucosa damage in AR rats.关键词
变应性鼻炎/山柰酚/细胞焦亡/TLR4/NF-κB/NLRP3通路Key words
Allergic rhinitis/Kaempferol/Pyroptosis/TLR4/NF-κB/NLRP3 pathway引用本文复制引用
李艳峰,王慧敏..山柰酚调控TLR4/NF-κB/NLRP3通路介导的细胞焦亡途径对变应性鼻炎大鼠的影响[J].中医药信息,2025,42(5):21-28,44,9.基金项目
河南省高等学校重点科研项目(23B320122) （23B320122）
