| 王蕾,金焕治,李飞静,黄杨锦.光甘草定通过NF-κB/iNOS信号轴抑制铁死亡改善缺氧诱导的心肌细胞损伤[J].浙江中西医结合杂志,2025,35(6): |
| 光甘草定通过NF-κB/iNOS信号轴抑制铁死亡改善缺氧诱导的心肌细胞损伤 |
| Glabridin ameliorates hypoxia-induced cardiomyocyte injury by inhibiting ferroptosis through NF-κB/iNOS signaling axis |
| 投稿时间：2024-08-14 修订日期：2025-04-17 |
| DOI： |
| 中文关键词: 光甘草定 NF-κB/iNOS信号通路 铁死亡 缺氧 心肌细胞损伤 |
| 英文关键词:Glabridin NF-κB/iNOS signaling pathway Ferroptosis Hypoxia Myocardial cell injury |
| 基金项目:温州市基础性公益科研项目(Y2023347) |
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| 摘要点击次数: 239 |
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| 中文摘要: |
| 目的 探究光甘草定(Glab)通过核因子-κB(NF-κB)/诱导性一氧化氮合酶(iNOS)信号轴调控铁死亡改善缺氧诱导的心肌细胞损伤的分子机制。方法 将H9c2细胞置于1% O2的缺氧培养箱中培养48 h,建立缺氧模型。将细胞随机分为对照组、缺氧组、缺氧+Glab-L组、缺氧+Glab-M组、缺氧+Glab-H组、缺氧+Erastin+Glab组(Erastin为铁死亡激动剂)、缺氧+PMA+Glab组(PMA为NF-κB信号通路激动剂),CCK-8检测细胞活力,流式细胞术检测细胞凋亡,采用乳酸脱氢酶(LDH)试剂盒、FerrorFarRed试剂盒、谷胱甘肽(GSH)试剂盒、丙二醛(MDA)试剂盒检测LDH、亚铁离子(Fe2+)、GSH、MDA含量,2",7"-二氯荧光素二乙酸酯(DCFH-DA)法检测活性氧(ROS)相对荧光强度,Western blot法检测谷胱甘肽过氧化物酶(GPX)4、长链酯酰辅酶A合成酶(ACSL)4、p65、磷酸化p65(p-p65)、iNOS表达水平。结果 与对照组相比,缺氧组细胞活力降低,LDH、ROS、MDA和Fe2+含量显著增加,GSH含量明显减少,细胞凋亡增多,ACSL4、p-p65和iNOS表达增加,GPX4表达减少；与缺氧组相比,缺氧+Glab-L组、缺氧+Glab-M组和缺氧+Glab-H组则逆转了上述现象,且呈现剂量依赖性；与缺氧+Glab组相比,缺氧+Erastin+Glab组细胞活力降低,细胞凋亡增加,LDH、ROS、MDA和Fe2+含量显著增加,GSH含量明显减少,ACSL4表达增加,GPX4表达减少；与缺氧+Glab组相比,缺氧+PMA+Glab组细胞活力降低,细胞凋亡增加,LDH、ROS、MDA和Fe2+含量显著增加,GSH含量明显减少,ACSL4、p-p65和iNOS表达增加,GPX4表达减少。结论 Glab通过调节NF-κB/iNOS信号通路抑制了H9c2细胞铁死亡和细胞凋亡,从而缓解了缺氧诱导的细胞损伤。 |
| 英文摘要: |
| Objective: To explore the molecular mechanism of glabridin (Glab) in improving hypoxia-induced myocardial cell injury by regulating ferroptosis through nuclear factor-κB (NF-κB)/inducible nitric oxide synthase (iNOS) signaling axis. Methods: H9c2 cells were cultured in a hypoxic incubator with 1% O2 for 48 hours to establish a hypoxic model. The cells were randomly divided into control group, hypoxia group, hypoxia + GLAB-L group, hypoxia + GLAB-M group, hypoxia + GLAB-H group, hypoxia +Erastin+Glab group (Erastin was ferroptosis agonist), hypoxia +PMA+Glab group (PMA was NF-κB signaling pathway agonist). CCK-8 was used to detect cell viability, and flow cytometry was used to detect cell apoptosis. Lactate dehydrogenase (LDH) kit, FerrorFarRed kit, glutathione (GSH) kit, and malondialdehyde (MDA) kit were used to detect LDH, ferrous ion (Fe2+), GSH and MDA content. The relative fluorescence intensity of reactive oxygen species (ROS) was detected by 2",7" -dichlorofluorescein diacetate (DCFH-DA) method. The expression levels of glutathione peroxidase (GPX) 4, long-chain acyl-coa synthetase (ACSL) 4, p65, phosphorylated p65 (p-p65) and iNOS were detected by Western blot. Results: Compared with the control group, the cell viability was decreased, LDH, ROS, MDA and Fe2+ contents were significantly increased, GSH content was significantly decreased, cell apoptosis was increased, the expression of ACSL4, p-p65 and iNOS was increased, and the expression of GPX4 was decreased in the hypoxia group. Compared with the hypoxia group, the above phenomena were reversed in a dose-dependent manner in the hypoxia +Glab-L, hypoxia +Glab-M and hypoxia +Glab-H groups. Compared with the hypoxia +Glab group, the cell viability of the hypoxia +Erastin+Glab group decreased, the cell apoptosis increased, the contents of LDH, ROS, MDA and Fe2+ increased, the GSH content decreased, the expression of ACSL4 increased, and the expression of GPX4 decreased. Compared with the hypoxia +Glab group, the hypoxia +PMA+Glab group showed decreased cell viability, increased cell apoptosis, increased LDH, ROS, MDA and Fe2+ contents, decreased GSH content, increased expression of ACSL4, p-p65 and iNOS, and decreased expression of GPX4. Conclusion: Glab inhibits ferroptosis and apoptosis in H9c2 cells by regulating the NF-κB/iNOS signaling pathway, thus alleviating hypoxia-induced cell damage. |
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