海南医科大学学报2026，Vol.32Issue(15)：1166-1174,9.DOI:10.13210/j.cnki.jhmu.20260525.001
基于SIRT1/Nrf2/HO-1介导的铁死亡探讨五味子乙素改善哮喘气道炎症的机制研究
Schisandrin B alleviates asthmatic airway inflammation by inhibiting ferroptosis via the SIRT1/Nrf2/HO-1 pathway
摘要
Abstract
Objective:To investigate the effects of Schisandrin B(Sch B)on ferroptosis,which is mediated by the SIRT1/Nrf2/HO-1 signaling pathway,and to elucidate its molecular mechanism in suppressing airway inflammation.Methods:An in vi-tro inflammatory model was established by stimulating human airway epithelial cells with lipopolysaccharide(LPS).The cell via-bility was measured using the cell counting kit-8(CCK-8)assay to determine the appropriate concentrations of Sch B for interven-tion.The cells were then divided into the following groups:control,model,low-dose Sch B(5 μmol/L),high-dose Sch B(10 μmol/L),and SIRT1 agonist(SRT1720)groups.The levels of interleukin(IL)-6,IL-8,MCP-1,and IL-33 were detected by ELISA.Intracellular reactive oxygen species(ROS)levels were assessed using the C11-BODIPY fluorescent probe.Mitochondri-al morphology was observed by transmission electron microscopy.The protein expression of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),SIRT1,nuclear and cytoplasmic nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was measured by Western blot.Intracellular Fe2+concentration and SIRT1 en-zyme activity were determined using commercial kits.The acetylation level of Nrf2 was examined by co-immunoprecipitation.Results:Compared with the control group,the model group showed significant increases in the release of inflammatory factors(IL-6,IL-8,MCP-1,and IL-33),ROS levels,ACSL4 protein expression,Fe2+concentration,and cytoplasmic Nrf2 protein ex-pression,along with significant decreases in GPX4,SIRT1,nuclear Nrf2,and HO-1 protein expression as well as SIRT1 en-zyme activity,all of which were statistically significant(P<0.01).Compared to the model group,Sch B treatment dose-dependently and significantly reversed the changes in the above indicators and reduced the acetylation level of Nrf2,with sta-tistical significance(P<0.01).Conclusion:Sch B may alleviate asthmatic airway inflammation by inhibiting ferroptosis in airway epithelial cells,which is likely mediated through the activation of the SIRT1/Nrf2/HO-1 signaling pathway.关键词
五味子乙素/哮喘/气道炎症/铁死亡/SIRT1Key words
Schisandrin B/Asthma/Airway inflammation/Ferroptosis/SIRT1分类
医药卫生引用本文复制引用
高鑫,田春燕,李竹英..基于SIRT1/Nrf2/HO-1介导的铁死亡探讨五味子乙素改善哮喘气道炎症的机制研究[J].海南医科大学学报,2026,32(15):1166-1174,9.基金项目
This study was supported by the Scientific Research Project of Heilongjiang Administration of Traditional Chinese Medicine(ZHY2025-207) 黑龙江省中医药科研项目(ZHY2025-207) （ZHY2025-207）
