中国病理生理杂志2025，Vol.41Issue(5)：909-918,10.DOI:10.3969/j.issn.1000-4718.2025.05.009
黄芩苷调节HIF-1α/SLC7A11/GPX4轴抑制ox-LDL诱导的巨噬细胞源性泡沫细胞形成
Baicalin modulates HIF-1α/SLC7A11/GPX4 axis to inhibit ox-LDL-in-duced ferroptosis in macrophage-derived foam cells
摘要
Abstract
AIM:This study aims to investigate the effects of baicalin on the hypoxia-inducible factor-1α(HIF-1α)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)axis and the ferroptosis induced by oxidized low-density lipoprotein(ox-LDL)in RAW264.7 macrophage-derived foam cells.METHODS:RAW264.7 cells were categorized into five groups:control,ox-LDL,baicalin+ox-LDL,ferrostatin-1(Fer-1;ferroptosis inhibitor)+ox-LDL,and baicalin+Fer-1+ox-LDL.To induce foam cell formation,RAW264.7 macrophages were exposed to 100 μg/mL ox-LDL for 24 h.Oil red O staining was employed to visualize lipid droplet formation in each group.The ultrastructure of the mitochondria was examined using transmission electron microscopy.Fluorescence microscopy was utilized to assess the fluorescence intensity of intracellular reactive oxygen species(ROS),lipid peroxides,and Fe2+.A colorimetric assay facilitated the measurement of malondialdehyde(MDA)and glutathione(GSH)levels.Additionally,Western blot analy-sis was conducted to quantify protein levels of HIF-1α,SLC7A11,and GPX4.RESULTS:The model group exhibited foam cell formation,abundant lipid droplets,significant swelling of mitochondrial structures,and observable shortening or disappearance of cristae.There was a marked increase in intracellular fluorescence intensity of ROS,lipid peroxides,and Fe2+,alongside elevated MDA levels and decreased GSH levels.HIF-1α protein expression was significantly increased,while SLC7A11 and GPX4 protein expressions were notably decreased(P<0.05).In comparison to the model group,both the baicalin+ox-LDL and Fer-1+ox-LDL groups demonstrated a significant reduction in lipid droplets,improved mitochon-drial structures,decreased fluorescence intensity of ROS,lipid peroxides,and Fe2+,as well as lower MDA levels and higher GSH levels.Additionally,HIF-1α expression significantly decreased,while SLC7A11 and GPX4 expressions sig-nificantly increased(P<0.05).Furthermore,the baicalin+Fer-1+ox-LDL group showed a more pronounced reduction in lipid droplets,near-normal mitochondrial structures,lower fluorescence intensity of ROS,lipid peroxides,and Fe2+,de-creased MDA levels,and increased GSH levels compared to the baicalin+ox-LDL group;HIF-1α,SLC7A11,and GPX4 protein expressions were also significantly reduced(P<0.05).CONCLUSION:Baicalin modulates the HIF-1α/SLC7A11/GPX4 axis,thereby inhibiting ox-LDL-induced ferroptosis in macrophage-derived foam cells.关键词
黄芩苷/动脉粥样硬化/泡沫细胞/铁死亡/HIF-1α/SLC7A11/GPX4轴Key words
baicalin/atherosclerosis/foam cells/ferroptosis/HIF-1α/SLC7A11/GPX4 axis分类
基础医学引用本文复制引用
于宁,宋囡,隋国媛,曹媛,贾连群..黄芩苷调节HIF-1α/SLC7A11/GPX4轴抑制ox-LDL诱导的巨噬细胞源性泡沫细胞形成[J].中国病理生理杂志,2025,41(5):909-918,10.基金项目
国家自然科学基金资助项目(No.82474221) （No.82474221）
辽宁省自然科学基金计划项目(博士科研启动项目)(No.2024-BS-142) （博士科研启动项目）
辽宁省教育厅高校基本科研项目(No.LJ232410162027) （No.LJ232410162027）
