中国药业2025，Vol.34Issue(20)：36-42,7.DOI:10.3969/j.issn.1006-4931.2025.20.009
茯苓酸通过NRF2/SLC7A11/GPX4铁死亡途径对慢性炎症性肠病模型小鼠的影响
Effect of Pachymic Acid on Chronic Inflammatory Bowel Disease in Model Mice Through NRF2/SLC7A11/GPX4 Ferroptosis Pathway
摘要
Abstract
Objective To investigate the effect of pachymic acid(PA)on dextran sulfate sodium(DSS)induced chronic inflammatory bowel disease(IBD)in model mice.Methods A total of 40 C57 BL/6J mice were randomly divided into the control group(equal volume of physiological saline),the model group(equal volume of physiological saline),and PA low-and high-dose groups(35 mg/kg,50 mg/kg),with 10 mice in each group.Drinking water containing 3%DSS freely to replicate mice model with chronic IBD.After successful modeling,mice were intraperitoneally injected corresponding drugs or physiological saline once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the morphology of colon tissue.Immunohistochemistry was used to analyze the expression levels of zonula occludens-1(ZO-1)and Occludin in colon tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of malondialdehyde(MDA),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and Fe2+was detected.Immunofluorescence method,RT-PCR and Western blot were used to detect the expression levels of key regulatory proteins of ferroptosis[glutathione peroxidase 4(GPX4),solute vector family 7 member 11(SLC7A11),nuclear transcription factor erythroid 2-related factor 2(NRF2)]in colon tissue.The possibility of PA binding to ferroptosis related regulatory proteins was verified by molecular docking method.Results Compared with the model group,the injury of intestinal mucosa in low-and high-dose PA groups was significantly improved,and the protein levels of ZO-1 and Occludin in colonic tissue were significantly increased(P<0.05);the levels of IL-1β,IL-6,TNF-α,MDA and Fe2+were significantly decreased(P<0.05),and the level of IL-10 was significantly increased(P<0.05);the fluorescence intensity of SLC7A11 and GPX4 were significantly increased(P<0.05);the mRNA and protein levels of NRF2,SLC7A11,GPX4 were significantly increased(P<0.05);PA combined with NRF2,SLC7A11,and GPX4 all showed strong binding energy(-9.42 kcal/mol,-9.216 kcal/mol,-5.497 kcal/mol).Conclusion PA can alleviate DSS induced chronic IBD in model mice by regulating NRF2/SLC7A11/GPX4 ferroptosis pathway.关键词
茯苓酸/炎症性肠病/铁死亡/NRF2/SLC7A11/GPX4/葡聚糖硫酸钠Key words
pachymic acid/inflammatory bowel disease/ferroptosis/NRF2/SLC7A11/GPX4/dextran sulfate sodium分类
医药卫生引用本文复制引用
鲁婵婵,李鹤,王诗韵,姜蕴沁,舒适,王灿,汤璐敏..茯苓酸通过NRF2/SLC7A11/GPX4铁死亡途径对慢性炎症性肠病模型小鼠的影响[J].中国药业,2025,34(20):36-42,7.基金项目
上海市浦东新区卫生健康委员会卫生科技项目[PW2024A-83] （）
上海市浦东新区健康委员会学科建设计划项目[PWZxk2022-11] （）
上海市浦东新区中医药传承创新发展示范试点项目[YC-2023-0610]. （）
