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OA
Schisandrin B alleviates asthmatic airway inflammation by inhibiting ferroptosis via the SIRT1/Nrf2/HO-1 pathway
目的:观察五味子乙素(Schisandrin B,Sch B)对沉默信息调节因子1/核因子红细胞2相关因子2/血红素氧合酶1(silent information regulator 1/nuclear factor erythroid 2-related factor 2/heme oxygenase 1,SIRT1/Nrf2/HO-1)信号通路介导的铁死亡的影响,从而阐明其抑制气道炎症的分子机制.方法:采用脂多糖(lipopolysaccharide,LPS)诱导人气道上皮细胞构建体外炎症模型.通过细胞计数试剂盒8(cell counting kit-8,CCK-8)法检测细胞活力并筛选Sch B干预浓度.随后设置空白组、模型组、Sch B低剂量组(5 μmol/L)、Sch B 高剂量组(10 μmol/L)及 SIRT1 激动剂组(SRT1720).采用 ELISA 法检测白细胞介素(interleukin,IL)-6、IL-8、人单核细胞趋化蛋白 1(monocyte chemotactic protein 1,MCP-1)和 IL-33 水平;C11-BODIPY荧光探针检测细胞内活性氧(reactive oxygen species,ROS)水平;透射电镜观察线粒体形态;Western blot检测 GPX4、ACSL4、SIRT1、核及胞质 Nrf2、HO-1蛋白表达;试剂盒检测细胞内 Fe2+浓度及SIRT1 酶活性;免疫共沉淀检测 Nrf2 乙酰化水平.结果:与空白组比较,模型组炎症因子(IL-6、IL-8、MCP-1、IL-33)释放、ROS水平、ACSL4蛋白表达、Fe2+浓度及细胞质 Nrf2蛋白表达均明显升高,GPX4、SIRT1、胞核Nrf2及HO-1蛋白表达、SIRT1酶活性均明显降低,差异均具有统计学意义(P<0.01).与模型组比较,Sch B干预能剂量依赖性地逆转上述指标的变化,并降低Nrf2乙酰化水平,差异均具有统计学意义(P<0.01).结论:五味子乙素可能通过激活SIRT1/Nrf2/HO-1信号通路,抑制气道上皮细胞的铁死亡,从而减轻哮喘气道炎症.
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.
高鑫;田春燕;李竹英
黑龙江中医药大学,黑龙江 哈尔滨,150040黑龙江中医药大学附属第一医院,黑龙江 哈尔滨,150040黑龙江中医药大学附属第一医院,黑龙江 哈尔滨,150040
医药卫生
五味子乙素哮喘气道炎症铁死亡SIRT1
Schisandrin BAsthmaAirway inflammationFerroptosisSIRT1
《海南医科大学学报》 2026 (15)
1166-1174,9
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)
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