中药新药与临床药理2025，Vol.36Issue(12)：2013-2023,11.DOI:10.19378/j.issn.1003-9783.2025.12.001
薏苡素调控IL-17A/NF-κB/MAPK信号通路对溃疡性结肠炎小鼠的作用及机制
Effects and Mechanisms of Coixol Modulating the IL-17A/NF-κB/MAPK Signaling Pathway to Alleviate Ulcerative Colitis in Mice
摘要
Abstract
Objective To investigate the effect and mechanism of coixol on ulcerative colitis(UC)in mice based on the interleukin-17A(IL-17A)-nuclear factor-κB(NF-κB)/mitogen-activated protein kinase(MAPK)signaling pathway.Methods C57BL/6J mice were randomly divided into normal group,model group,mesalazine group(600 mg·kg-1),and coixol low-dose(25 mg·kg-1)and high-dose(50 mg·kg-1)groups,with 10 mice per group.The normal group was given distilled water,while the other groups received 2%DSS solution ad libitum on weeks 1,4,and 7.From week 4,the drug groups were administered by gavage at the above doses,while the normal and model groups received 0.5%CMC-Na solution(10 mg·kg-1)once daily for 4 weeks.General conditions were observed,fecal occult blood was detected,and disease activity index(DAI)and body mass loss rate were calculated.Serum levels of IL-6,IL-8,IL-1β,TNF-α,IL-10,lipopolysaccharide(LPS),and myeloperoxidase(MPO)were measured by ELISA.Hematoxylin-eosin(HE)and Alcian blue-periodic acid-Schiff(AB-PAS)staining were used to observe colonic pathological changes and goblet cell count.Wheat germ agglutinin(WGA)staining was applied to assess mucin secretion.Transmission electron microscopy was used to observe colonic ultrastructure.qRT-PCR and Western Blot were retrospectively employed to detect mRNA and protein expression of IL-17A,IL-17RA,Act1,TRAF6,NF-κB,IKBα,and p38 MAPK in colonic tissue.Results Compared with the normal group,the model group showed lethargy,sluggish movement,dull fur,hunched posture,diarrhea,and bloody stools;significant decreases in body mass and colon length(P＜0.01),increased DAI score(P＜0.01);elevated serum IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO levels(P＜0.01),decreased IL-10(P＜0.01);epithelial damage,crypt distortion,diffuse inflammatory infiltration in mucosa and submucosa,and increased pathological score(P＜0.01);reduced and scattered goblet cells with decreased area proportion(P＜0.01)and mucin secretion(P＜0.01);disordered epithelial cell arrangement,irregular microvilli,vacuolation,mitochondrial swelling,cristae damage,and widened intercellular junctions;upregulated mRNA expression of IL-17A,IL-17RA,Act1,TRAF6,NF-κB,and p38 MAPK(P＜0.01),downregulated IKBα mRNA(P＜0.01);increased protein expression of IL-17A,IL-17RA,Act1,TRAF6,p-NF-κB/NF-κB,p-IKBα/IKBα,and p-p38 MAPK/p38 MAPK(P＜0.01).Compared with the model group,all treatment groups showed improved mental state,glossier fur,reduced diarrhea and bloody stools;increased body mass(P＜0.05,P＜0.01)and colon length(P＜0.01),decreased DAI score(P＜0.01);reduced serum IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO(P＜0.05,P＜0.01),increased IL-10(P＜0.01);restored epithelial and crypt structure,reduced inflammatory infiltration and pathological score(P＜0.05,P＜0.01);increased goblet cell count and area proportion(P＜0.01),enhanced mucin secretion(P＜0.05,P＜0.01);improved epithelial cell alignment,regular microvilli,reduced vacuolation,alleviated mitochondrial swelling,restored cristae structure,and narrowed intercellular junctions;downregulated mRNA expression of IL-17A,IL-17RA,Act1,TRAF6,NF-κB,and p38 MAPK(P＜0.05,P＜0.01),upregulated IKBα mRNA(P＜0.01);decreased protein expression of IL-17A,IL-17RA,Act1,TRAF6,p-NF-κB/NF-κB,p-IKBα/IKBα,and p-p38 MAPK/p38 MAPK(P＜0.05,P＜0.01).Conclusion Coixol can repair intestinal mucosal damage,inhibit inflammatory cell infiltration,protect colonic structural integrity,and regulate inflammatory factors in UC mice,potentially by suppressing the IL-17A/NF-κB/MAPK signaling pathway.关键词
薏苡素/溃疡性结肠炎/IL-17A/NF-κB/MAPK信号通路/炎症反应/小鼠Key words
coixol/ulcerative colitis/IL-17A/NF-κB/MAPK signaling pathway/inflammatory response/mice分类
医药卫生引用本文复制引用
陈健,魏智祥,安嘉琪,李丹彤,顾颖,李丽,张一昕..薏苡素调控IL-17A/NF-κB/MAPK信号通路对溃疡性结肠炎小鼠的作用及机制[J].中药新药与临床药理,2025,36(12):2013-2023,11.基金项目
国家自然科学基金青年基金项目(82003913) （82003913）
河北省自然科学基金项目(H2024206502) （H2024206502）
河北省教育厅科技项目(BJK2024082). （BJK2024082）
