缺氧诱导因子调控的铁死亡及其在胃肠道疾病中的作用研究进展

来源期刊：广州医药 | 16-23 发布时间：2026-01-20 收稿时间：2026/2/6 15:10:30 阅读量：41

作者：: 牛孟迪,

赵思羽,

赵澈,

肖莉,

孙丽新,

关键词：: 铁死亡缺氧诱导因子结直肠癌溃疡性结肠炎胃癌; ferroptosis hypoxia-inducible factors colorectal cancer ulcerative colitis gastric cancer

DOI：: 10. 20223 / j. cnki. 1000-8535. 2026. 01. 003

收稿时间：: 2025-06-29
修订日期：
接收日期：
引用总数：: 0

铁死亡是一种以铁依赖性脂质过氧化为特征的程序性细胞死亡形式。近年来研究表明，铁死亡与缺氧应答的关键调控因子——缺氧诱导因子（HIF）存在密切关联。HIF（包括HIF-1α、HIF-2α、HIF-3α三种亚型）调控的铁死亡在结直肠癌、胃癌、溃疡性结肠炎及其他胃肠黏膜损伤性疾病中发挥作用，影响疾病的发生发展。但目前关于HIF-铁死亡通路在不同胃肠道疾病中的差异化作用及调控机制尚未完全阐明。因此，本文对HIF各亚型调控铁死亡的分子机制及其在胃肠道疾病中的作用进行综述，以期为靶向HIF-铁死亡通路治疗相关疾病提供新的思路。

铁死亡是一种区别于凋亡、坏死和自噬的新型程序性细胞死亡形式，它的发现为疾病机制研究和治疗策略开发提供了新视角^［1-2］。病理条件下的缺氧微环境可通过激活缺氧诱导因子（hypoxia-inducible factor，HIF）调控细胞代谢与应激反应^［3］。近年来的研究表明，HIF可通过靶向铁死亡相关通路影响疾病进展，深入研究其调控机制，不仅有助于延缓疾病进展，还可为药物开发提供新靶点。本文综述HIF调控铁死亡的分子机制及其在胃肠道疾病中的作用，以期为疾病治疗提供理论依据。

1 铁死亡概述

铁死亡是一种新型程序性细胞死亡方式，其核心机制涉及三大方面：铁稳态失衡、脂质过氧化和氧化应激^［4］。具体而言，铁超载通过芬顿反应催化活性氧（reactive oxygen species，ROS）生成，诱导细胞膜脂质过氧化，最终引发铁死亡。脂质过氧化物在Fe²⁺的催化下破坏细胞膜与细胞器膜结构，导致膜流动性、通透性改变及其他级联反应。同时，氧化应激通过调节铁死亡相关蛋白的表达与活性，调控细胞对铁死亡的敏感性^［5］。因此，调控铁代谢或抗氧化防御能力可显著影响铁死亡敏感性。

2 HIF 调控铁死亡的分子网络

HIF是由氧敏感α亚基（HIF-1α、HIF-2α、HIF-3α）和组成型β亚基（HIF-1β）构成的异二聚体转录因子。常氧条件下，脯氨酰羟化酶（prolyl hydroxylase domain protein，PHD）介导HIF-α羟基化，促进其与冯·希佩尔-林道（von Hippel-Lindau，VHL）蛋白结合并通过泛素化途径降解。缺氧条件下，PHD失活，HIF-α稳定并进入细胞核，与HIF-1β形成异二聚体，结合靶基因的缺氧反应元件（hypoxia response element，HRE），激活靶基其转录^［3，6］。这些基因的表达可以调控铁死亡的发生，且不同HIF-α亚型对铁死亡的调控作用存在差异。

2.1 HIF-1α

HIF-1α对铁死亡的调控主要涉及三个方面。影响代谢重编程：（1）在肿瘤细胞中，HIF-1α通过上调乳酸脱氢酶（lactate dehydrogenase，LDH）等糖酵解关键蛋白，驱动代谢重编程，促进氧化磷酸化向糖酵解的转变，导致乳酸积累和胞内pH降低，进而以pH依赖的方式抑制铁死亡^［7］。（2）在透明细胞肾细胞癌中，VHL蛋白突变引发HIF-1α组成性激活，上调己糖激酶2（hexokinase 2，HK2），增强糖酵解；同时，赖氨酸去甲基化酶5C（lysine demethylase 5C，KDM5C）的缺失会上调葡萄糖-6-磷酸脱氢酶（glucose-6-phosphate dehydrogenase，G6PD），促进还原型烟酰胺腺嘌呤二核苷酸磷酸（reduced nicotinamide adenine dinucleotide phosphate，NADPH）生成，促进糖代谢重编程，增强抗氧化能力并抑制铁死亡，从而诱导化疗耐药^［8］。（3）在肺泡上皮细胞中，HIF-1α通过上调烯醇化酶1（enolase 1，ENO1）促进糖酵解，抑制氧化磷酸化并增加ROS生成，影响了糖代谢重编程，最终通过氧化应激加剧铁死亡，导致急性肺损伤^［9］。（4）在缺血再灌注损伤后的大脑中，HIF-1α与信号转导及转录激活因子3（signal transducer and activator of transcription 3，STAT3）协同激活聚合酶I和转录释放因子（polymerase I and transcript release factor，PTRF），后者通过稳定磷脂酶A2组蛋白4A（phospholipase A2，group IVA，PLA2G4A）促进脂质代谢重编程，破坏线粒体能量稳态并加速氧化损伤，最终诱发铁死亡，导致缺血性脑卒中^［10］。

影响铁代谢与氧化还原状态：（1）在肝癌、胃癌、结直肠癌（colorectal cancer，CRC）、鼻咽癌、膀胱癌、肝纤维化、脑缺血再灌注损伤及溃疡性结肠炎模型中，上调溶质载体家族7成员11（solute carrier family 7 member 11，SLC7A11）、谷氨酸转运蛋白（solute carrier family 1 member 1，SLC1A1）、谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）表达，增加胱氨酸摄取，促进谷胱甘肽（glutathione，GSH）合成，从而减少ROS积累并抑制铁死亡^{［7，11-21］}（2）上调转铁蛋白受体（transferrin receptor，TFR）表达，增加细胞铁摄取并加剧氧化应激，进而提高铁死亡敏感性^{［18，22-25］}。（3）下调乙酰辅酶A合成酶长链家族4（acyl-CoA synthetase long chain family 4，ACSL4）的表达，减少脂质过氧化，抑制铁死亡^［26-28］。（4）调控血红素加氧酶（heme oxygenase-1，HO-1）表达：过度激活HO-1会导致铁过载并诱导铁死亡^［29-36］，而适度激活HO-1则可维持氧化还原平衡^［37］。（5）抑制核受体辅激活因子4（nuclear receptor coactivator 4，NCOA4）介导的铁蛋白自噬，减少胞内游离铁释放，抑制铁死亡而并导致疾病进展^［38-39］。

影响血管内皮生长因子的表达：上调血管内皮生长因子（vascular endothelial growth factor，VEGF）达来表达间接调控细胞铁死亡的敏感性，但具体分子机制尚未完全阐明。目前研究提示，VEGF的促血管生成作用可能通过改组氧气供应、减少氧化应激和ROS积累，从而降低铁死亡风险^［40］。然而，这一上述假说需通过实验研究进一步验证。

2.2 HIF-2α

HIF-2α对铁死亡的调控呈现双向性，其作用受细胞、组织、疾病类型等因素共同影响，提示靶向HIF-2α铁死亡治疗法需结合细胞微环境的具体特征。

在特定细胞类型（如巨噬细胞、肾癌细胞）中，HIF-2α的激活可通过影响铁代谢来抑制铁死亡。人巨噬细胞和纤维肉瘤细胞共培养后发现，HIF-2α促进铜蓝蛋白（ceruloplasmin，CP）mRNA在巨噬细胞中表达，随后CP mRNA被转移到人纤维肉瘤细胞中，mRNA被翻译成蛋白，从而以促进铁输出，细胞内铁浓度下降，抑制铁死亡^［41］。透明细胞肾细胞癌中，线粒体铁硫簇组装蛋白2水平降低会阻断铁反应元件依赖性翻译，降低HIF-2α蛋白水平，干扰铁代谢，增加细胞对铁死亡的敏感性，抑制肿瘤生长，间接证明HIF-2α对铁死亡的抑制作用^［42］。

在缺氧以及病理损伤（如炎症、钙化、毒素影响）情况下，HIF-2α激活，通过铁代谢、脂代谢、氧化应激促进铁死亡。在溃疡性结肠结直肠癌CRC小鼠模型中，HIF-2α的表达上调使二价金属离子转运蛋白1（divalent metal transporter 1，DMT1）表达升高，ROS升高，细胞内铁增加，促进铁死亡^［43-44］。在椎间盘退变小鼠模型中，软骨终板的钙化会加剧椎间盘内的缺氧微环境，HIF-2α表达上调，促进TFR表达，细胞内铁浓度升高，促进铁死亡^［45］。在砷诱导的人肾上皮细胞和肾损伤小鼠模型中，HIF-2α激活促进双氧化酶1表达升高，ROS升高，促进铁死亡^［46］。人肺动脉平滑肌细胞和肺动脉高压大鼠模型中，缺氧导致HIF-2α激活，并伴随自噬发生，导致MPO和ROS积累，促进铁死亡^［47］。

2.3 HIF-3α

与HIF-1α和HIF-2α相比，HIF-3α的调控能尚不未明确。目前仅有一项针对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的研究表明，COPD患者肺组织中的HIF-3α与GPX4表达呈正相关性，其表达下调可能加剧肺泡上皮细胞铁死亡^［48］。然而，HIF-3α是否直接通过转录调控GPX4表达仍有待验证，且其在其他组织或疾病中铁死亡调控的普适性尚未探索。该发现提示HIF-3α-GPX4轴可能成为COPD中铁死亡的潜在调控靶点，但需通一步实验研究明确其分子互作机制。

综上，HIF各亚型调控铁代谢、抗氧化及脂质过氧化通路影响铁死亡的作用存在异同，其关键信号通路见图1。HIF-1α和HIF-2α均可通过调节糖酵解、线粒体功能或脂质代谢来改变能量代谢状态，间接影响铁死亡敏感性。HIF-1α的作用高度复杂，通过代谢重编程、铁代谢、氧化还原稳态双向调控铁死亡，在肿瘤中多表现为抑制铁死亡。HIF-2α以促进铁死亡为主，但在某些特定细胞中通过输出铁以抑制铁死亡，具有微环境依赖性。HIF-3α调控铁死亡的研究较少，其在胃肠道等疾病中的具体作用尚缺乏直接证据，是未来研究需要关注的方向。深入研究HIF亚型在不同组织中的特异性调控网络，对疾病治疗具有重要意义。

图 1 HIF 调控铁死亡的关键信号通路

注：LPCAT：溶血磷脂酰胆碱酰基转移酶；Cys-Cys：胱氨酸；Cys：半胱氨酸；PUFAs：多不饱和脂肪酸；PUFAs-CoA：多饱和脂肪酰辅酶A；PUFAs-PL：多不饱和脂肪酸磷脂；PUFAs-PL-OOH：多不饱和脂肪酸磷脂氢过氧化物；PUFAs-PL-OH：多不饱和脂肪磷脂醇。

3 HIF- 铁死亡轴在胃肠道疾病中的作用

HIF在肠道中表达广泛，在维持肠道屏障功能、调节免疫反应、促进组织修复方面发挥重要作用^［49-53］。在胃癌组织中HIF由于肿瘤细胞快速增殖引发的局部缺氧而显著上调^［54］。因此，病理条件下，HIF的表达变化会影响胃肠道细胞对铁死亡的敏感性，靶向HIF调控的铁死亡有望对胃肠道疾病发挥治疗作用。

3.1 结直肠癌

CRC是全球癌症相关死亡的主要原因之一［55］，其进展与HIF-α调控的铁死亡密切相关。HIF-1α抑制CRC细胞铁死亡。在癌CRC细胞（HCT116、SW620）和小癌CRC细胞（MC38、CT26）中，淫羊藿苷可以与高迁移率族蛋白A2（high mobility group A2，HMGA2）、STAT3、HIF-1α蛋白结合，下调HIF-1α并抑制SLC7A11和GPX4的表达，阻断抗氧化防御系统，从而诱导铁死亡。此外淫羊藿苷可以通过诱导线粒体膜电位下降、ATP生成减少及嵴结构破坏，导致ROS蓄积与脂质过氧化，协同增强铁死亡敏感性。值得注意的是，淫羊藿苷联合程序性死亡受体1（programmed death-1，PD-1）抑制剂可激活CD8⁺ T细胞分泌干扰素-γ（interferon-gamma，IFN-γ），后者通过STAT1信号通路抑制SLC7A11和GPX4表达，建立免疫与铁死亡的协同调控机制，重塑肿瘤免疫微环境^［21］。

HIF-2α促进CRC细胞铁死亡。在CRC细胞系（HCT116、SW480）中，HIF-2α稳定剂罗沙司他（roxadustat）通过上调缺氧诱导脂滴相关蛋白（hypoxia inducible lipid droplet associated protein，HILPDA）和围脂滴蛋白2（perilipin 2，PLIN2），促进脂质过氧化。在SLC7A11缺失癌CRC模型中，HIF-2α过表达导致结肠组织铁蓄积及4-羟基-2-壬烯醛（4-hydroxy-2-nonenal，4-HNE）、ROS水平升高，协同诱导铁死亡^［44］。因此，抑癌CRC发展可以利用天然化合物（如淫羊藿苷）或小分子抑制剂阻断HIF-1α通路，逆转癌细胞的铁死亡抵抗；也可以将铁死亡诱导剂与免疫检查点抑制剂（如PD-1抑制剂）联用，通过激活CD8⁺ T细胞-IFN-γ轴增强疗效；还可以通过稳定HIF-2α或抑制其负调控因子，增强癌细胞的铁死亡敏感性以抑制肿瘤发展。

3.2 胃癌

胃癌是全球第五大常见癌症和第三大癌症死亡原因，其中腹膜是胃癌转移的常见部位^［56］。HIF-1α抑制GC细胞铁死亡。胃癌腹膜转移灶的缺氧微环境可上调HIF-1α表达，进而激活腹膜转移相关长链非编码RNA（peritoneal metastasis associated long noncoding RNA，NPMAN）-PMAN的转录。PMAN与胚胎致死异常视觉样蛋白1（embryonic lethal abnormal vision-like 1，ELAVL1）直接结合，促进其向细胞质转位。胞质ELAVL1通过结合SLC7A11 mRNA的3'-UTR区域增强其稳定性，进而促进GSH合成，减低ROS及铁离子蓄积，最终抑制铁死亡并促进肿瘤细胞存活，推动腹膜转移^［14］。

因此，未来可通过抑制HIF-1α进而下调PMAN表达，诱导铁死亡，抑制腹膜转移进程。值得注意的是，目前RNA类药物受限于递送效率和稳定性，未来研究应聚焦小分子抑制剂或肽类药物的开发，以实现更高效的靶向干预。

3.3 溃疡性结肠炎

溃疡性结肠炎（ulcerative colitis，UC）是一种以肠道上皮屏障损伤、菌群失调和免疫紊乱为特征的炎症性肠病^［57］。近年研究表现，UC患者肠上皮细胞铁死亡可破坏肠道屏障完整性并加剧炎症反应，而中药活性成分可通过调控铁死亡与肠道菌群互作来缓解病理进程。

HIF-1α可抑制结肠部位的铁死亡。HIF-1α表达升高可改善体外肠上皮细中炎症因子的分泌和铁死亡，这种作用与GPX4基因的转录激活有关，HIF-1α通过上调GPX4的表达以抑制小鼠结肠上皮细胞的铁死亡，进而改善肠道屏障功能，缓解UC^［19-20］。研究发现，在葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的UC小鼠模型中，中药活性成分川陈皮素可直接与HIF-1α结合，增强其稳定性和活性，上调结肠部位的GPX4、SLC7A11的表达，下调ACSL4表达，减少脂质过氧化，进而抑制肠上皮细胞的铁死亡^［20］。

HIF-2α可促进结肠铁死亡。在UC患者结肠组织中，HIF-2α的激活与疾病进展密切相关［58］。在DSS或三硝基苯磺酸（trinitrobenzenesulfonic acid，TNBS）诱导的UC小鼠模型中，高脂饮食通过增加肠道菌群代谢产物脱氧胆酸（deoxycholic acid，DCA）水平，协同缺氧微环境激活HIF-2α，进而上调DMT1、ACSL4表达并抑制GPX4表达，导致铁超载、GSH耗竭及脂质过氧化标志物丙二醛（malondialdehyde，MDA）积累，最终通过铁死亡加剧结肠炎症。该机制在脂多糖（lipopolysaccharide，LPS）诱导的人结肠腺癌细胞（Caco-2）和大鼠小肠隐窝上皮细胞（IEC-6）模型中得了验证且肠特异性HIF-2α基因敲的小鼠实验证实，HIF-2α缺失可显著改善铁死亡相关指标及炎症表型。该研究还发现，在DSS诱导的结肠炎小鼠及LPS诱导的Caco-2细胞中，从当归中分离出的白当归素（byakangelicin，BKG）可阻断DCA与HIF-2α的结合，抑制铁死亡并缓解炎症，但其分子互作机制仍需探究^［43］。

因此，通过优化中药单体结构增强HIF-1α稳定性或调节肠道菌群代谢物、或开剂靶向HIF-2α的小分子抑制剂，降低结肠炎患者结肠部位的铁死亡，有望成为UC治疗的新方向。

3.4 其他

HIF-1α、HIF-2α促进铁死亡而导致缺氧引发的胃肠黏膜损伤。

缺氧诱导的胃肠黏膜损伤模型中，HIF-1α、HIF-2α继而诱导烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（nicotinamide adenine dinucleotide phosphate oxidase 4，NOX4）和花生四烯酸5-脂氧合酶（arachidonate 5-lipoxygenase，ALOX5）高表达，驱动ROS生成及脂质过氧化，增强铁死亡敏感性并加剧黏膜损伤。研究发现，口服刺槐花外泌体纳米颗粒可以下调小鼠胃肠黏膜中的HIF-1α、ROS、4-HNE及过氧化脂质（lipid peroxide，LPO）水平，抑制铁死亡并缓解黏膜损伤，但不影响HIF-2α蛋白表达。而在人胃黏膜上皮细胞（NGEC）和肠上皮细胞（HIEC）中，该纳米颗粒可同时下调HIF-1α和HIF-2α表达，抑制NOX4和ALOX5的表达并减少ROS介导的脂质过氧化，从而保护细胞免受铁死亡损伤^［59］。

刺槐花外泌体纳米颗粒具备低毒性和高生物相容性的优势，是靶向HIF-α治疗胃肠黏膜损伤的潜在候选药物。然而，其在不同物种细胞中调控HIF的差异性提示需在临床前研究中充分考虑个体化治疗策略。未来研究需优化纳米颗粒的靶向递送效率，并探索其联合用药方案以提升疗效。

4 总结与展望

近年来，铁死亡在多种疾病中的作用逐渐受到关注，尤其是在缺氧环境下， HIF与铁死亡的调控关系渐成为研究热点。在胃肠道疾病中，缺氧较为常见，HIF通过调控铁死亡在胃肠道疾病中发挥双重作用：抑制肿瘤细胞铁死亡以促进疾病发展，而诱导正常细胞铁死亡则会加剧炎症损伤。未来研究应聚焦于：（1）探索HIF-3α的调控网络及其与铁死亡的分子关联；（2）开发靶向特定HIF-α亚型的药物，以应对其功能异质性；（3）优化中药活性成分（如淫羊藿苷、白当归素）与纳米递送系统的协同策略，提升疗效并降低毒性；（4）整合HIF与其他信号通路的交互作用，构建更全面的分子调控网络。

1、JIANG%E2%80%83X%EF%BC%8CSTOCKWELL%E2%80%83B%E2%80%83R%EF%BC%8CCONRAD%E2%80%83M%EF%BC%8E%0AFerroptosis%EF%BC%9AMechanisms%EF%BC%8Cbiology%E2%80%83and%E2%80%83role%E2%80%83in%E2%80%83disease%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Rev%E2%80%83Mol%E2%80%83Cell%E2%80%83Biol%EF%BC%8C2021%EF%BC%8C22%EF%BC%884%EF%BC%89%EF%BC%9A%0A266-282%EF%BC%8E

2、季鹏，王祥龙，葛健文，等．铁死亡诱导药物及其抗癌机制研究进展［J］．中国药理学与毒理学杂志，2022，36（6）：473-480．

3、KAELIN%E2%80%83W%E2%80%83J%EF%BC%8CRATCLIFFE%E2%80%83P%E2%80%83J%EF%BC%8EOxygen%E2%80%83sensing%E2%80%83by%E2%80%83%0Ametazoans%EF%BC%9AThe%E2%80%83central%E2%80%83%20role%E2%80%83of%E2%80%83the%E2%80%83HIF%E2%80%83%20hydroxylase%E2%80%83%0Apathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8EMol%E2%80%83Cell%EF%BC%8C2008%EF%BC%8C30%EF%BC%884%EF%BC%89%EF%BC%9A393-402%EF%BC%8E

4、TOCKWELL%E2%80%83B%E2%80%83R%EF%BC%8CFRIEDMANN%E2%80%83ANGELI%E2%80%83J%E2%80%83P%E2%80%83F%EF%BC%8C%0ABAYIR%E2%80%83H%EF%BC%8Cet%E2%80%83al%EF%BC%8EFerroptosis%EF%BC%9AA%E2%80%83regulated%E2%80%83cell%E2%80%83death%E2%80%83%0Anexus%E2%80%83linking%E2%80%83metabolism%EF%BC%8Credox%E2%80%83biology%EF%BC%8Cand%E2%80%83disease%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%EF%BC%8C2017%EF%BC%8C171%EF%BC%882%EF%BC%89%EF%BC%9A273-285%EF%BC%8E

5、DIXON%E2%80%83S%E2%80%83J%EF%BC%8COLZMANN%E2%80%83J%E2%80%83A%EF%BC%8EThe%E2%80%83%20cell%E2%80%83%20biology%E2%80%83%20of%E2%80%83%0Aferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Rev%E2%80%83Mol%E2%80%83Cell%E2%80%83Biol%EF%BC%8C2024%EF%BC%8C25%0A%EF%BC%886%EF%BC%89%EF%BC%9A424-442%EF%BC%8E

6、OHH%E2%80%83M%20%EF%BC%8C%20PARK%E2%80%83C%E2%80%83W%20%EF%BC%8C%20IVAN%E2%80%83M%20%EF%BC%8C%20et%E2%80%83al%20%EF%BC%8E%0AUbiquitination%E2%80%83%20of%E2%80%83%20hypoxia-inducible%E2%80%83factor%E2%80%83%20requires%E2%80%83%0Adirect%E2%80%83binding%E2%80%83to%E2%80%83the%E2%80%83beta-domain%E2%80%83of%E2%80%83the%E2%80%83von%E2%80%83Hippel%02Lindau%E2%80%83protein%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Cell%E2%80%83Biol%EF%BC%8C2000%EF%BC%8C2%0A%EF%BC%887%EF%BC%89%EF%BC%9A423-427%EF%BC%8E

7、YANG%E2%80%83Z%EF%BC%8CSU%E2%80%83W%EF%BC%8CWEI%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-1%CE%B1%E2%80%83%20drives%E2%80%83%0Aresistance%E2%80%83to%E2%80%83ferroptosis%E2%80%83in%E2%80%83solid%E2%80%83tumors%E2%80%83by%E2%80%83promoting%E2%80%83%0Alactate%E2%80%83production%E2%80%83and%E2%80%83activating%E2%80%83SLC1A1%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83%0ARep%EF%BC%8C2023%EF%BC%8C42%EF%BC%888%EF%BC%89%EF%BC%9A112945%EF%BC%8E

8、ZHENG%E2%80%83Q%EF%BC%8CLI%E2%80%83P%EF%BC%8CZHOU%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EDeficiency%E2%80%83%20of%E2%80%83%0Athe%E2%80%83X-inactivation%E2%80%83%20escaping%E2%80%83%20gene%E2%80%83KDM5C%E2%80%83in%E2%80%83%20clear%E2%80%83%0Acell%E2%80%83%20renal%E2%80%83cell%E2%80%83carcinoma%E2%80%83%20promotes%E2%80%83tumorigenicity%E2%80%83%20by%E2%80%83%0Areprogramming%E2%80%83%20glycogen%E2%80%83metabolism%E2%80%83%20and%E2%80%83inhibiting%E2%80%83%0Aferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ETheranostics%EF%BC%8C2021%EF%BC%8C11%EF%BC%8818%EF%BC%89%EF%BC%9A%0A8674-8691%EF%BC%8E

9、ZHANG%E2%80%83H%EF%BC%8CWU%E2%80%83D%EF%BC%8CWANG%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EMETTL3-%0Amediated%E2%80%83N6-methyladenosine%E2%80%83exacerbates%E2%80%83ferroptosis%E2%80%83%0Avia%E2%80%83m6A-IGF2BP2-dependent%E2%80%83mitochondrial%E2%80%83metabolic%E2%80%83%0Areprogramming%E2%80%83in%E2%80%83sepsis-induced%E2%80%83acute%E2%80%83lung%E2%80%83injury%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EClin%E2%80%83Transl%E2%80%83Med%EF%BC%8C%E2%80%832023%EF%BC%8C13%EF%BC%889%EF%BC%89%EF%BC%9Ae1389%EF%BC%8E

10、JIN%E2%80%83W%EF%BC%8CZHAO%E2%80%83J%EF%BC%8CYANG%E2%80%83E%EF%BC%8Cet%E2%80%83al%EF%BC%8ENeuronal%E2%80%83STAT3%2F%0AHIF-1%CE%B1%2FPTRF%E2%80%83axis-mediated%E2%80%83bioenergetic%E2%80%83disturbance%E2%80%83%0Aexacerbates%E2%80%83cerebral%E2%80%83ischemia-reperfusion%E2%80%83injury%E2%80%83via%E2%80%83%0APLA2G4A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ETheranostics%EF%BC%8C2022%EF%BC%8C12%EF%BC%887%EF%BC%89%EF%BC%9A%0A3196-3216%EF%BC%8E

11、%E2%80%83%20FAN%E2%80%83Z%EF%BC%8CYANG%E2%80%83G%EF%BC%8CZHANG%E2%80%83W%EF%BC%8Cet%E2%80%83al%EF%BC%8EHypoxia%E2%80%83%0Ablocks%E2%80%83ferroptosis%E2%80%83%20of%E2%80%83%20hepatocellular%E2%80%83%20carcinoma%E2%80%83%20via%E2%80%83%0Asuppression%E2%80%83of%E2%80%83METTL14%E2%80%83triggered%E2%80%83YTHDF2-%0Adependent%E2%80%83silencing%E2%80%83of%E2%80%83SLC7A11%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Cell%E2%80%83Mol%E2%80%83%0AMed%EF%BC%8C2021%EF%BC%8C25%EF%BC%8821%EF%BC%89%EF%BC%9A10197-10212%EF%BC%8E

12、YUAN%E2%80%83S%EF%BC%8CWEI%E2%80%83C%EF%BC%8CLIU%E2%80%83G%EF%BC%8Cet%E2%80%83al%EF%BC%8ES%20o%20r%20af%20e%20ni%20b%E2%80%83%0Aattenuates%E2%80%83liver%E2%80%83fibrosis%E2%80%83by%E2%80%83triggering%E2%80%83hepatic%E2%80%83%20stellate%E2%80%83%0Acell%E2%80%83ferroptosis%E2%80%83via%E2%80%83HIF-1%CE%B1%2FSLC7A11%E2%80%83pathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACell%E2%80%83Prolif%EF%BC%8C2022%EF%BC%8C55%EF%BC%881%EF%BC%89%EF%BC%9Ae13158%EF%BC%8E

13、LI%E2%80%83Y%EF%BC%8CYANG%E2%80%83W%EF%BC%8CZHENG%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8ETargeting%E2%80%83fatty%E2%80%83%0Aacid%E2%80%83%20synthase%E2%80%83modulates%E2%80%83%20sensitivity%E2%80%83of%E2%80%83%20hepatocellular%E2%80%83%0Acarcinoma%E2%80%83to%E2%80%83sorafenib%E2%80%83via%E2%80%83ferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Exp%E2%80%83%0AClin%E2%80%83Cancer%E2%80%83Res%EF%BC%8C2023%EF%BC%8C42%EF%BC%881%EF%BC%89%EF%BC%9A6%EF%BC%8E

14、LIN%E2%80%83Z%EF%BC%8CSONG%E2%80%83J%EF%BC%8CGAO%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EHypoxia-induced%E2%80%83%0AHIF-1%CE%B1%2FlncRNA-PMAN%E2%80%83%20inhibits%E2%80%83%20ferroptosis%E2%80%83%20by%E2%80%83%0Apromoting%E2%80%83the%E2%80%83cytoplasmic%E2%80%83translocation%E2%80%83of%E2%80%83ELAVL1%E2%80%83in%E2%80%83%0Aperitoneal%E2%80%83dissemination%E2%80%83from%E2%80%83gastric%E2%80%83cancer%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ARedox%E2%80%83Biol%EF%BC%8C2022%EF%BC%8852%EF%BC%89%EF%BC%9A102312%EF%BC%8E

15、LU%E2%80%83X%EF%BC%8CLI%E2%80%83D%EF%BC%8CLIN%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-1%CE%B1-induced%E2%80%83%0Aexpression%E2%80%83of%E2%80%83the%E2%80%83m6A%E2%80%83%20reader%E2%80%83YTHDF1%E2%80%83inhibits%E2%80%83the%E2%80%83%0Aferroptosis%E2%80%83%20of%E2%80%83%20nucleus%E2%80%83%20pulposus%E2%80%83%20cells%E2%80%83%20by%E2%80%83%20promoting%E2%80%83%0ASLC7A11%E2%80%83translation%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAging%E2%80%83Cell%EF%BC%8C2024%EF%BC%8C23%0A%EF%BC%889%EF%BC%89%EF%BC%9Ae14210%EF%BC%8E

16、%E2%80%83%20CAI%E2%80%83W%EF%BC%8CWU%E2%80%83S%EF%BC%8CLIN%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8EHypoxia-induced%E2%80%83%0ABAP1%E2%80%83%20enhances%E2%80%83%20erastin-induced%E2%80%83%20ferroptosis%E2%80%83%20in%E2%80%83%0Anasopharyngeal%E2%80%83carcinoma%E2%80%83by%E2%80%83stabilizing%E2%80%83H2A%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACancer%E2%80%83Cell%E2%80%83Int%EF%BC%8C2024%EF%BC%8C24%EF%BC%881%EF%BC%89%EF%BC%9A307%EF%BC%8E

17、YAN%E2%80%83Y%EF%BC%8CHUANG%E2%80%83Z%EF%BC%8CZHU%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8EIMP2%E2%80%83%20drives%E2%80%83%0Achemoresistance%E2%80%83%20by%E2%80%83%20repressing%E2%80%83%20cisplatin-induced%E2%80%83%0Aapoptosis%E2%80%83and%E2%80%83ferroptosis%E2%80%83via%E2%80%83activation%E2%80%83of%E2%80%83%20IPO4%E2%80%83and%E2%80%83%0ASLC7A11%E2%80%83under%E2%80%83hypoxia%E2%80%83in%E2%80%83bladder%E2%80%83cancer%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACancer%E2%80%83Cell%E2%80%83Int%EF%BC%8C2024%EF%BC%8C24%EF%BC%881%EF%BC%89%EF%BC%9A386%EF%BC%8E

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19、HU%E2%80%83W%EF%BC%8CCAI%E2%80%83Y%EF%BC%8CCAI%E2%80%83D%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-1%CE%B1%E2%80%83alleviates%E2%80%83%0Aferroptosis%E2%80%83in%E2%80%83ulcerative%E2%80%83colitis%E2%80%83by%E2%80%83regulation%E2%80%83of%E2%80%83GPX4%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Death%E2%80%83Dis%EF%BC%8C2025%EF%BC%8C16%EF%BC%881%EF%BC%89%EF%BC%9A542%EF%BC%8E

20、CHEN%E2%80%83Z%EF%BC%8CHUANG%E2%80%83G%EF%BC%8CFANG%E2%80%83G%EF%BC%8Cet%E2%80%83al%EF%BC%8ENobiletin%E2%80%83%0Aregulates%E2%80%83gut%E2%80%83microbiota%E2%80%83and%E2%80%83mediates%E2%80%83HIF-1%CE%B1%E2%80%83to%E2%80%83%0Aalleviate%E2%80%83DSS-induced%E2%80%83ulcerative%E2%80%83colitis%E2%80%83by%E2%80%83inhibiting%E2%80%83%0Aferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Agric%E2%80%83Food%E2%80%83Chem%EF%BC%8C2025%EF%BC%8C73%0A%EF%BC%8831%EF%BC%89%EF%BC%9A19427-19441%EF%BC%8E

21、%E2%80%83%20WANG%E2%80%83H%EF%BC%8CSUN%E2%80%83K%EF%BC%8CSHAN%E2%80%83T%E2%80%83W%EF%BC%8Cet%E2%80%83al%EF%BC%8EIcariin%E2%80%83%0Apromoted%E2%80%83%20ferroptosis%E2%80%83%20by%E2%80%83%20activating%E2%80%83%20mitochondrial%E2%80%83%0Ady%20sf%20u%20nctio%20n%E2%80%83%20to%E2%80%83%20i%20n%20hi%20bit%E2%80%83%20colo%20rectal%E2%80%83%20ca%20nce%20r%E2%80%83%20a%20n%20d%E2%80%83%0Asynergistically%E2%80%83enhanced%E2%80%83the%E2%80%83efficacy%E2%80%83of%E2%80%83PD-1%E2%80%83inhibitors%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EPhytomedicine%EF%BC%8C2025%EF%BC%88136%EF%BC%89%EF%BC%9A156224%EF%BC%8E

22、SANGUIGNO%E2%80%83L%EF%BC%8CGUIDA%E2%80%83N%EF%BC%8CANZILOTTI%E2%80%83S%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AStroke%E2%80%83by%E2%80%83inducing%E2%80%83HDAC9-dependent%E2%80%83deacetylation%E2%80%83%0Aof%E2%80%83HIF-1%E2%80%83and%E2%80%83Sp1%EF%BC%8Cpromotes%E2%80%83TfR1%E2%80%83transcription%E2%80%83and%E2%80%83%0AGPX4%E2%80%83reduction%EF%BC%8Cthus%E2%80%83determining%E2%80%83ferroptotic%E2%80%83neuronal%E2%80%83%0Adeath%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83J%E2%80%83Biol%E2%80%83Sci%EF%BC%8C2023%EF%BC%8C19%EF%BC%889%EF%BC%89%EF%BC%9A2695-%0A2710%EF%BC%8E

23、YANG%E2%80%83L%EF%BC%8CLIU%E2%80%83Q%EF%BC%8CLU%E2%80%83Q%EF%BC%8Cet%E2%80%83al%EF%BC%8EScavenger%E2%80%83%20receptor%E2%80%83%0Aclass%E2%80%83B%E2%80%83type%E2%80%83%20I%E2%80%83%20deficiency%E2%80%83induces%E2%80%83iron%E2%80%83overload%E2%80%83and%E2%80%83%0Aferroptosis%E2%80%83in%E2%80%83renal%E2%80%83tubular%E2%80%83epithelial%E2%80%83cells%E2%80%83via%E2%80%83hypoxia%02inducible%E2%80%83factor-1alpha%2Ftransferrin%E2%80%83receptor%E2%80%831%E2%80%83signaling%E2%80%83%0Apathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAntioxid%E2%80%83Redox%E2%80%83Signal%EF%BC%8C2024%EF%BC%8C41%0A%EF%BC%881-3%EF%BC%89%EF%BC%9A56-73%EF%BC%8E

24、%E2%80%83LI%E2%80%83Y%EF%BC%8CCAO%E2%80%83Y%EF%BC%8CXIAO%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EI%20n%20hi%20bit%20o%20r%E2%80%83%20of%E2%80%83%0Aapoptosis-stimulating%E2%80%83protein%E2%80%83of%E2%80%83p53%E2%80%83inhibits%E2%80%83ferroptosis%E2%80%83%0Aand%E2%80%83alleviates%E2%80%83intestinal%E2%80%83ischemia%2Freperfusion-induced%E2%80%83%0Aacute%E2%80%83lung%E2%80%83injury%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Death%E2%80%83Differ%EF%BC%8C2020%EF%BC%8C27%0A%EF%BC%889%EF%BC%89%EF%BC%9A2635-2650%EF%BC%8E

25、%E2%80%83%20CHEN%E2%80%83B%E2%80%83Y%EF%BC%8CPATHAK%E2%80%83J%E2%80%83L%EF%BC%8CLIN%E2%80%83H%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AInflammation%E2%80%83triggers%E2%80%83chondrocyte%E2%80%83ferroptosis%E2%80%83in%E2%80%83TMJOA%E2%80%83%0Avia%E2%80%83HIF-1%CE%B1%2FTFRC%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Dent%E2%80%83Res%EF%BC%8C2024%EF%BC%8C103%0A%EF%BC%887%EF%BC%89%EF%BC%9A712-722%EF%BC%8E

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28、PAN%E2%80%83G%EF%BC%8CXIA%E2%80%83Y%EF%BC%8CHAO%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8EEZH2%E2%80%83suppresses%E2%80%83%0AIR-induced%E2%80%83ferroptosis%E2%80%83%20by%E2%80%83forming%E2%80%83%20a%E2%80%83%20co-repressor%20complex%E2%80%83with%E2%80%83HIF-1%CE%B1%E2%80%83to%E2%80%83inhibit%E2%80%83ACSL4%EF%BC%9ATargeting%E2%80%83%0AEZH2%E2%80%83enhances%E2%80%83%20radiosensitivity%E2%80%83in%E2%80%83KDM6A-deficient%E2%80%83%0Aesophageal%E2%80%83squamous%E2%80%83carcinoma%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Death%E2%80%83%0ADiffer%EF%BC%8C2025%EF%BC%8C32%EF%BC%886%EF%BC%89%EF%BC%9A1026-1040%EF%BC%8E

29、%E2%80%83%20SHI%E2%80%83J%EF%BC%8CWANG%E2%80%83Q%E2%80%83H%EF%BC%8CWEI%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EHistone%E2%80%83%0Aacetyltransferase%E2%80%83P300%E2%80%83deficiency%E2%80%83promotes%E2%80%83ferroptosis%E2%80%83%0Aof%E2%80%83%20vascular%E2%80%83%20smooth%E2%80%83%20muscle%E2%80%83%20cells%E2%80%83%20by%E2%80%83%20activating%E2%80%83the%E2%80%83%0AHIF-1%CE%B1%2FHMOX1%E2%80%83axis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EMol%E2%80%83Med%EF%BC%8C2023%EF%BC%8C29%0A%EF%BC%881%EF%BC%89%EF%BC%9A91%EF%BC%8E

30、%E2%80%83WU%E2%80%83Y%20%EF%BC%8C%20WANG%E2%80%83J%20%EF%BC%8C%20ZHAO%E2%80%83T%20%EF%BC%8C%20et%E2%80%83al%20%EF%BC%8E%20Di-%0A%EF%BC%882-ethylhexyl%EF%BC%89phthalate%E2%80%83exposure%E2%80%83leads%E2%80%83to%E2%80%83ferroptosis%E2%80%83%0Avia%E2%80%83the%E2%80%83HIF-1%CE%B1%2FHO-1%E2%80%83%20signaling%E2%80%83%20pathway%E2%80%83in%E2%80%83mouse%E2%80%83%0Atestes%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Hazard%E2%80%83Mater%EF%BC%8C2022%EF%BC%88426%EF%BC%89%EF%BC%9A127807%EF%BC%8E

31、LU%E2%80%83C%EF%BC%8CZHANG%E2%80%83Z%EF%BC%8CFAN%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EShikonin%E2%80%83induces%E2%80%83%0Aferroptosis%E2%80%83in%E2%80%83osteosarcomas%E2%80%83through%E2%80%83the%E2%80%83mitochondrial%E2%80%83%0AROS-regulated%E2%80%83HIF-1%CE%B1%2FHO-1%E2%80%83axis%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0APhytomedicine%EF%BC%8C2024%EF%BC%88135%EF%BC%89%EF%BC%9A156139%EF%BC%8E

32、GONG%E2%80%83Q%EF%BC%8CLAI%E2%80%83T%EF%BC%8CLIANG%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8ETa%20rgeted%E2%80%83%0Ainhibition%E2%80%83of%E2%80%83CX3CL1%E2%80%83limits%E2%80%83%20podocytes%E2%80%83ferroptosis%E2%80%83to%E2%80%83%0Aameliorate%E2%80%83cisplatin-induced%E2%80%83acute%E2%80%83kidney%E2%80%83injury%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AMol%E2%80%83Med%EF%BC%8C2023%EF%BC%8C29%EF%BC%881%EF%BC%89%EF%BC%9A140%EF%BC%8E

33、%E2%80%83%20LI%E2%80%83R%EF%BC%8CWANG%E2%80%83X%EF%BC%8CZHANG%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-1%CE%B1%2FHO-%0A1-mediated%E2%80%83ferroptosis%E2%80%83%20participates%E2%80%83in%E2%80%83%20polystyrene%E2%80%83%0Ananoplastics-induced%E2%80%83intergenerational%E2%80%83cardiotoxicity%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENano%E2%80%83Lett%EF%BC%8C2025%EF%BC%8C25%EF%BC%886%EF%BC%89%EF%BC%9A2226-2235%EF%BC%8E

34、WU%E2%80%83Y%EF%BC%8CWANG%E2%80%83J%EF%BC%8CZHAO%E2%80%83T%EF%BC%8Cet%E2%80%83al%EF%BC%8EPolystyrenenan%02oplastics%E2%80%83lead%E2%80%83to%E2%80%83ferroptosis%E2%80%83in%E2%80%83the%E2%80%83lungs%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Adv%E2%80%83%0ARes%EF%BC%8C2024%EF%BC%8856%EF%BC%89%EF%BC%9A31-41%EF%BC%8E

35、%E2%80%83%20ZHENG%E2%80%83S%EF%BC%8CJIANG%E2%80%83J%EF%BC%8CSHU%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8EFine%E2%80%83particulate%E2%80%83%0Amatter%EF%BC%88PM2%EF%BC%8E5%EF%BC%89induces%E2%80%83testosterone%E2%80%83disruption%E2%80%83by%E2%80%83%0Atriggering%E2%80%83ferroptosis%E2%80%83through%E2%80%83SIRT1%2FHIF-1%CE%B1%E2%80%83signaling%E2%80%83%0Apathway%E2%80%83in%E2%80%83male%E2%80%83mice%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFree%E2%80%83Radic%E2%80%83Biol%E2%80%83Med%EF%BC%8C%0A2024%EF%BC%88221%EF%BC%89%EF%BC%9A40-51%EF%BC%8E

36、%E2%80%83YANG%E2%80%83Y%EF%BC%8CLIU%E2%80%83M%EF%BC%8CDONG%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8ENa%20ringin%E2%80%83%0Asuppresses%E2%80%83CoCl2-induced%E2%80%83ferroptosis%E2%80%83in%E2%80%83ARPE-%0A19%E2%80%83cells%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAntioxidants%EF%BC%88Basel%EF%BC%89%EF%BC%8C2025%EF%BC%8C14%0A%EF%BC%882%EF%BC%89%EF%BC%9A236%EF%BC%8E

37、LIU%E2%80%83Y%EF%BC%8CCUI%E2%80%83H%EF%BC%8CMEI%E2%80%83C%EF%BC%8Cet%E2%80%83al%EF%BC%8ESirtuin4%E2%80%83alleviates%E2%80%83%0Asevere%E2%80%83acute%E2%80%83pancreatitis%E2%80%83by%E2%80%83regulating%E2%80%83HIF-1%CE%B1%2FHO-1%E2%80%83%0Amediated%E2%80%83ferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Death%E2%80%83Dis%EF%BC%8C2023%0A%EF%BC%8814%EF%BC%89%EF%BC%9A694%EF%BC%8E

38、GAO%E2%80%83Y%EF%BC%8CTONG%E2%80%83M%EF%BC%8CWONG%E2%80%83T%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8ELong%E2%80%83%0Anoncoding%E2%80%83RNA%E2%80%83URB1-antisense%E2%80%83RNA%E2%80%831%EF%BC%88AS1%EF%BC%89%0As%20u%20p%20p%20re%20s%20se%20s%E2%80%83%20so%20rafe%20ni%20b-i%20n%20d%20uce%20d%E2%80%83%20fe%20r%20ro%20pto%20si%20s%E2%80%83%20i%20n%E2%80%83%0Ahepatocellular%E2%80%83%20carcinoma%E2%80%83%20by%E2%80%83%20driving%E2%80%83ferritin%E2%80%83%20phase%E2%80%83separation%EF%BC%BBJ%EF%BC%BD%EF%BC%8EACS%E2%80%83Nano%EF%BC%8C2023%EF%BC%8C17%EF%BC%8822%EF%BC%89%EF%BC%9A%0A22240-22258%EF%BC%8E

39、NI%E2%80%83S%EF%BC%8CYUAN%E2%80%83Y%EF%BC%8CQIAN%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8EHypoxia%E2%80%83inhibits%E2%80%83%0ARANKL-induced%E2%80%83ferritinophagy%E2%80%83and%E2%80%83protects%E2%80%83osteoclasts%E2%80%83%0Afrom%E2%80%83ferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFree%E2%80%83Radic%E2%80%83Biol%E2%80%83Med%EF%BC%8C2021%0A%EF%BC%88169%EF%BC%89%EF%BC%9A271-282%EF%BC%8E

40、%E2%80%83%20ZHU%E2%80%83Y%EF%BC%8CHOU%E2%80%83H%EF%BC%8CLI%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EHyperoxia%E2%80%83exposure%E2%80%83%0Ainduces%E2%80%83ferroptosis%E2%80%83and%E2%80%83apoptosis%E2%80%83%20by%E2%80%83%20downregulating%E2%80%83%0APLAGL2%E2%80%83and%E2%80%83repressing%E2%80%83HIF-1%CE%B1%2FVEGF%E2%80%83%20signaling%E2%80%83%0Apathway%E2%80%83in%E2%80%83newborn%E2%80%83alveolar%E2%80%83typeII%E2%80%83epithelial%E2%80%83cell%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ARedox%E2%80%83Rep%EF%BC%8C2024%EF%BC%8C29%EF%BC%881%EF%BC%89%EF%BC%9A2387465%EF%BC%8E

41、%E2%80%83%20SCHWANTES%E2%80%83A%EF%BC%8CWICKERT%E2%80%83A%EF%BC%8CBECKER%E2%80%83S%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0ATumor%E2%80%83associated%E2%80%83macrophages%E2%80%83transfer%E2%80%83ceruloplasmin%E2%80%83%0AmRNA%E2%80%83to%E2%80%83fibrosarcoma%E2%80%83%20cells%E2%80%83%20and%E2%80%83%20protect%E2%80%83them%E2%80%83from%E2%80%83%0Aferroptosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ERedox%E2%80%83Biol%EF%BC%8C2024%EF%BC%8871%EF%BC%89%EF%BC%9A103093%EF%BC%8E

42、GREEN%E2%80%83Y%E2%80%83S%EF%BC%8CFERREIRA%E2%80%83DOS%E2%80%83SANTOS%E2%80%83M%E2%80%83C%EF%BC%8CFUJA%E2%80%83%0AD%E2%80%83G%EF%BC%8Cet%E2%80%83al%EF%BC%8EISCA2%E2%80%83inhibition%E2%80%83%20decreases%E2%80%83%20HIF%E2%80%83%20and%E2%80%83%0Ainduces%E2%80%83ferroptosis%E2%80%83in%E2%80%83clear%E2%80%83cell%E2%80%83renal%E2%80%83carcinoma%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AOncogene%EF%BC%8C2022%EF%BC%8C41%EF%BC%8842%EF%BC%89%EF%BC%9A4709-4723%EF%BC%8E

43、WANG%E2%80%83C%EF%BC%8CCHU%E2%80%83Q%EF%BC%8CDONG%E2%80%83W%EF%BC%8Cet%E2%80%83al%EF%BC%8EMicrobial%E2%80%83%0Ametabolite%E2%80%83%20deoxycholic%E2%80%83%20acid-mediated%E2%80%83ferroptosis%E2%80%83%0Aexacerbates%E2%80%83high-fat%E2%80%83diet-induced%E2%80%83colonic%E2%80%83inflammation%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EMol%E2%80%83Metab%EF%BC%8C2024%EF%BC%8884%EF%BC%89%EF%BC%9A101944%EF%BC%8E

44、%E2%80%83%20SINGHAL%E2%80%83R%EF%BC%8CMITTA%E2%80%83S%E2%80%83R%EF%BC%8CDAS%E2%80%83N%E2%80%83K%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-%0A2%CE%B1%E2%80%83%20activation%E2%80%83%20potentiates%E2%80%83%20oxidative%E2%80%83%20cell%E2%80%83%20death%E2%80%83in%E2%80%83%0Acolorectal%E2%80%83cancers%E2%80%83by%E2%80%83increasing%E2%80%83cellular%E2%80%83iron%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83%0AClin%E2%80%83Invest%EF%BC%8C2021%EF%BC%8C131%EF%BC%8812%EF%BC%89%EF%BC%9Ae143691%EF%BC%8E

45、JING%E2%80%83X%EF%BC%8CWANG%E2%80%83W%EF%BC%8CHE%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-2%CE%B1%2FTFR1%E2%80%83%0Amediated%E2%80%83%20iron%E2%80%83%20homeostasis%E2%80%83%20disruption%E2%80%83%20aggravates%E2%80%83%0Acartilage%E2%80%83%20endplate%E2%80%83%20degeneration%E2%80%83through%E2%80%83ferroptotic%E2%80%83%0Adamage%E2%80%83and%E2%80%83mtDNA%E2%80%83release%EF%BC%9AA%E2%80%83%20new%E2%80%83mechanism%E2%80%83%20of%E2%80%83%0Aintervertebral%E2%80%83disc%E2%80%83degeneration%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83%20Orthop%E2%80%83%0ATranslat%EF%BC%8C2024%EF%BC%8846%EF%BC%89%EF%BC%9A65-78%EF%BC%8E

46、YANG%E2%80%83D%EF%BC%8CXIA%E2%80%83X%EF%BC%8CXI%E2%80%83S%EF%BC%8ESalvianolic%E2%80%83acid%E2%80%83A%E2%80%83attenuates%E2%80%83%0Aarsenic-induced%E2%80%83ferroptosis%E2%80%83and%E2%80%83kidney%E2%80%83injury%E2%80%83via%E2%80%83HIF-%0A2%CE%B1%2FDUOX1%2FGPX4%E2%80%83and%E2%80%83iron%E2%80%83homeostasis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ESci%E2%80%83%0ATotal%E2%80%83Environ%EF%BC%8C2024%EF%BC%88907%EF%BC%89%EF%BC%9A168073%EF%BC%8E

47、%E2%80%83%20WANG%E2%80%83E%EF%BC%8CZHANG%E2%80%83B%EF%BC%8CHUANG%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8ELncRNA%E2%80%83%0AMIR210HG%E2%80%83promotes%E2%80%83phenotype%E2%80%83switching%E2%80%83of%E2%80%83pulmonary%E2%80%83%0Aarterial%E2%80%83smooth%E2%80%83muscle%E2%80%83cells%E2%80%83through%E2%80%83autophagy%02dependent%E2%80%83ferroptosis%E2%80%83pathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8EApoptosis%EF%BC%8C%0A2024%EF%BC%8C29%EF%BC%889-10%EF%BC%89%EF%BC%9A1648-1662%EF%BC%8E

48、%E2%80%83%20JIANG%E2%80%83J%EF%BC%8CZHENG%E2%80%83Z%EF%BC%8CCHEN%E2%80%83S%EF%BC%8Cet%E2%80%83al%EF%BC%8EHypoxia%E2%80%83%0Ainducible%E2%80%83factor%EF%BC%88HIF%EF%BC%893%CE%B1%E2%80%83%20prevents%E2%80%83%20COPD%E2%80%83%20by%E2%80%83%0Ainhibiting%E2%80%83alveolar%E2%80%83epithelial%E2%80%83cell%E2%80%83ferroptosis%E2%80%83via%E2%80%83the%E2%80%83%0AHIF-3%CE%B1-GPx4%E2%80%83axis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ETheranostics%EF%BC%8C2024%EF%BC%8C14%0A%EF%BC%8814%EF%BC%89%EF%BC%9A5512-5527%EF%BC%8E

49、%E2%80%83%20GLOVER%E2%80%83L%E2%80%83E%EF%BC%8CSCOTT%E2%80%83LEE%E2%80%83J%EF%BC%8CCOLGAN%E2%80%83S%E2%80%83P%EF%BC%8E%0AOxygen%E2%80%83%20metabolism%E2%80%83%20and%E2%80%83%20barrier%E2%80%83%20regulation%E2%80%83in%E2%80%83the%E2%80%83%0Aintestinal%E2%80%83mucosa%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Clin%E2%80%83Invest%EF%BC%8C2016%EF%BC%8C126%0A%EF%BC%8810%EF%BC%89%EF%BC%9A3680-3688%EF%BC%8E

50、XIAO%E2%80%83J%EF%BC%8CGUO%E2%80%83X%EF%BC%8CWANG%E2%80%83Z%EF%BC%8ECrosstalk%E2%80%83%20between%E2%80%83%0Ahypoxia-inducible%E2%80%83factor-1%CE%B1%E2%80%83and%E2%80%83%20short-chain%E2%80%83fatty%E2%80%83%0Aacids%E2%80%83in%E2%80%83inflammatory%E2%80%83bowel%E2%80%83disease%EF%BC%9AKey%E2%80%83clues%E2%80%83toward%E2%80%83%0Aunraveling%E2%80%83the%E2%80%83mystery%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Immunol%EF%BC%8C2024%0A%EF%BC%8815%EF%BC%89%EF%BC%9A1385907%EF%BC%8E

51、RAMAKRISHNAN%E2%80%83S%E2%80%83K%EF%BC%8CSHAH%E2%80%83Y%E2%80%83M%EF%BC%8ERole%E2%80%83%20of%E2%80%83%0Aintestinal%E2%80%83HIF-2%CE%B1%E2%80%83in%E2%80%83health%E2%80%83and%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAnnu%E2%80%83%0ARev%E2%80%83Physiol%EF%BC%8C2016%EF%BC%8878%EF%BC%89%EF%BC%9A301-325%EF%BC%8E

52、%E2%80%83%20PRAL%E2%80%83L%E2%80%83P%EF%BC%8CFACHI%E2%80%83J%E2%80%83L%EF%BC%8CCORREA%E2%80%83R%E2%80%83O%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AHypoxia%E2%80%83and%E2%80%83HIF-1%E2%80%83as%E2%80%83key%E2%80%83regulators%E2%80%83of%E2%80%83gut%E2%80%83microbiota%E2%80%83%0Aand%E2%80%83host%E2%80%83interactions%EF%BC%BBJ%EF%BC%BD%EF%BC%8ETrends%E2%80%83Immunol%EF%BC%8C2021%EF%BC%8C%0A42%EF%BC%887%EF%BC%89%EF%BC%9A604-621%EF%BC%8E

53、赵雨晨，黄琛．炎症性肠病相关易感基因及其作用机制的研究进展［J］．广州医药，2025，56（3）：300-309．

54、GRIFFITHS%E2%80%83E%E2%80%83A%EF%BC%8CPRITCHARD%E2%80%83S%E2%80%83A%EF%BC%8CWELCH%E2%80%83%20I%E2%80%83%0AM%EF%BC%8Cet%E2%80%83al%EF%BC%8EIs%E2%80%83the%E2%80%83%20hypoxia-inducible%E2%80%83factor%E2%80%83%20pathway%E2%80%83%0Aimportant%E2%80%83in%E2%80%83gastric%E2%80%83cancer%EF%BC%BBJ%EF%BC%BD%EF%BC%8EEur%E2%80%83J%E2%80%83Cancer%EF%BC%8C%0A2005%EF%BC%8C41%EF%BC%8818%EF%BC%89%EF%BC%9A2792-2805%EF%BC%8E

55、%E2%80%83%20BRAY%E2%80%83F%EF%BC%8CLAVERSANNE%E2%80%83M%EF%BC%8CSUNG%E2%80%83H%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AGlobal%E2%80%83cancer%E2%80%83statistics%E2%80%832022%EF%BC%9AGLOBOCAN%E2%80%83estimates%E2%80%83%0Aof%E2%80%83incidence%E2%80%83and%E2%80%83mortality%E2%80%83worldwide%E2%80%83for%E2%80%8336%E2%80%83cancers%E2%80%83in%E2%80%83%0A185%E2%80%83countries%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECA%E2%80%83Cancer%E2%80%83J%E2%80%83Clin%EF%BC%8C2024%EF%BC%8C74%0A%EF%BC%883%EF%BC%89%EF%BC%9A229-263%EF%BC%8E

56、SMYTH%E2%80%83E%E2%80%83C%EF%BC%8CNILSSON%E2%80%83M%EF%BC%8CGRABSCH%E2%80%83H%E2%80%83I%EF%BC%8C%0Aet%E2%80%83al%EF%BC%8EGastric%E2%80%83cancer%EF%BC%BBJ%EF%BC%BD%EF%BC%8ELancet%EF%BC%8C2020%EF%BC%8C396%0A%EF%BC%8810251%EF%BC%89%EF%BC%9A635-648%EF%BC%8E

57、LE%E2%80%83BERRE%E2%80%83C%EF%BC%8CHONAP%E2%80%83S%EF%BC%8CPEYRIN-BIROULET%E2%80%83%0AL%EF%BC%8EUlcerative%E2%80%83colitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ELancet%EF%BC%8C2023%EF%BC%8C402%0A%EF%BC%8810401%EF%BC%89%EF%BC%9A571-584%EF%BC%8E

58、%E2%80%83%20BHAT%E2%80%83S%EF%BC%8CRIEDER%E2%80%83F%EF%BC%8EHypoxia-inducible%E2%80%83factor%E2%80%83%0A1-alpha%E2%80%83%20stabilizers%E2%80%83in%E2%80%83the%E2%80%83treatment%E2%80%83of%E2%80%83inflammatory%E2%80%83%0Abowel%E2%80%83diseases%EF%BC%9AOxygen%E2%80%83as%E2%80%83a%E2%80%83novel%E2%80%83IBD%E2%80%83therapy%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AJ%E2%80%83Crohns%E2%80%83Colitis%EF%BC%8C2022%EF%BC%8C16%EF%BC%8812%EF%BC%89%EF%BC%9A1924-1932%EF%BC%8E

59、WANG%E2%80%83D%EF%BC%8CZHANG%E2%80%83H%EF%BC%8CLIAO%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EO%20ral%E2%80%83%0Aadministration%E2%80%83of%E2%80%83Robinia%E2%80%83pseudoacacia%E2%80%83L%EF%BC%8Eflower%E2%80%83%0Aexosome-like%E2%80%83%20nanoparticles%E2%80%83%20attenuates%E2%80%83%20gastric%E2%80%83%20and%E2%80%83%0Asmall%E2%80%83intestinal%E2%80%83mucosal%E2%80%83ferroptosis%E2%80%83caused%E2%80%83by%E2%80%83hypoxia%E2%80%83%0Athrough%E2%80%83inhibiting%E2%80%83HIF-1%CE%B1-%E2%80%83and%E2%80%83HIF-2%CE%B1-mediated%E2%80%83%0Alipid%E2%80%83peroxidation%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Nanobiotechnology%EF%BC%8C%0A2024%EF%BC%8C22%EF%BC%881%EF%BC%89%EF%BC%9A479%EF%BC%8E

1、国家自然科学基金（82074115）；浙江省基础公益研究计划（LGN21C020002）()