溃疡性结肠炎（ulcerative colitis，UC）是一种以结肠黏膜慢性复发性炎症为特征的炎症性肠病，其发病机制涉及黏膜屏障破坏、免疫稳态失衡及多种应激性细胞死亡过程。近年来，铁依赖性脂质过氧化驱动的程序性细胞死亡——铁死亡（ferroptosis），以及以未折叠蛋白反应（unfolded protein response，UPR）为核心的内质网应激（endoplasmic reticulum stress， ERS），被认为在UC发生发展中发挥关键作用。大量研究证实，在UC患者及实验性结肠炎模型中，结肠组织存在铁稳态紊乱、脂质过氧化物蓄积、谷胱甘肽（glutathione，GSH）耗竭及谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）失活等铁死亡特征；药理或遗传学抑制铁死亡可显著减轻黏膜损伤和炎症反应。与此同时，肠上皮细胞中ERS持续激活，表现为内质网分子伴侣（glucose-regulated protein 78，GRP78）功能耗竭、C/EBP同源蛋白（C/EBP homologous protein，CHOP）和X盒结合蛋白1（X-box binding protein 1，XBP1）信号异常增强，其失衡可直接导致杯状细胞丢失和屏障功能破坏。值得注意的是，铁死亡与ERS并非独立事件，而是在UC炎症微环境中形成相互促进的病理网络：ERS可通过消耗GSH、放大氧化应激而增强铁死亡敏感性；反之，铁死亡产生的大量氧化脂质及损伤相关分子又可反向加重ERS，形成恶性循环。基于此，靶向铁死亡—ERS轴的干预策略，尤其是结合纳米递送系统实现精准调控，正逐渐成为UC治疗研究的重要方向。

Ulcerative colitis （UC） represents a specific manifestation of inflammatory bowel disease， which is distinguished by the chronic and recurrent inflammation of the colonic mucosa. The pathogenesis of UC encompasses the disruption of the intestinal mucosal barrier， the dysregulation of immune homeostasis， and the activation of multiple stress-related cell death pathways. In recent years， mounting evidence has demonstrated that ferroptosis， a type of regulated cell death propelled by iron-dependent lipid peroxidation， and endoplasmic reticulum stress （ERS）， mainly mediated by the unfolded protein response （UPR）， assume crucial roles in the onset and progression of UC. Research has revealed that colonic tissues obtained from patients with UC and experimental colitis models display dysregulated iron homeostasis， the accumulation of lipid peroxides， the depletion of glutathione （GSH）， and the inactivation of glutathione peroxidase 4 （GPX4）， all of which are characteristic hallmarks of ferroptosis. It has been reported that pharmacological or genetic inhibition of ferroptosis can mitigate mucosal injury and inflammatory responses. Meanwhile， the persistent activation of ERS in intestinal epithelial cells is evident， as indicated by the functional exhaustion of the endoplasmic reticulum chaperone glucose - regulated protein 78 （GRP78） and the enhanced signaling of C/EBP homologous protein （CHOP） and X-box binding protein 1 （XBP1）. Dysregulated ERS can directly lead to goblet cell loss and the impairment of epithelial barrier function. Significantly， ferroptosis and ERS are not independent processes but interact with each other within the inflammatory microenvironment of UC. ERS can enhance cellular susceptibility to ferroptosis by depleting GSH and intensifying oxidative stress. Conversely， excessive lipid peroxides and damage-associated molecular patterns produced during ferroptosis may further exacerbate ERS， thus forming a detrimental feedback loop. Therefore， therapeutic strategies targeting the ferroptosis-ERS axis， especially those integrated with nanotechnology-based delivery systems for precise regulation， might represent a promising approach for the treatment of UC.