Ulcerative colitis (UC) is an inflammatory disease characterized by an uncontrolled inflammatory response. Previous study showed that the immunological impairment elicted the alteration of inflammatory mediators, and ferroptosis was implicated with the lethal accumulation of reactive oxygen species (ROS). Therefore, this study aimed to investigate the role of ferroptosis in dextran sulfate sodium (DSS)-induced UC. The animal model was established and the molecular markers of ferroptosis were detected by using western blot. The results suggested that the expression of COX2 and ACSL4 was increased dramatically, while the level of GPX4 and FTH1 was deceased in 3% DSS group compared with Control group (P < 0.05). Meanwhile, the body weight and colon length were significantly increased, and the inflammation indexes and MDA levels were reduced in 3% DSS+ ferrostatin-1 group, 3% DSS+ liproxstatin-1 group and 3% DSS+ deferprone group compared to 3% DSS group (P < 0.05). Additionally, the mRNA and protein level of COX2 and ACSL4 were obviously upregulated, but the GPX4 and FTH1 expression were downregulated in 3% DSS group (P < 0.05); however, the expression level of COX2, ACSL4, GPX4 and FTH1 was revered after ferrostatin-1, liproxstatin-1 (Lip-1) or deferprone (DFP) administration. The immunohistochemical assay showed that the staining intensity of COX2 was decreased and the staining intensity of GPX4 was increased in 3% DSS+ Ferr-1 group compared with 3% DSS group (P < 0.05). Moreover, the nuclear factor erythoid 2-related 2 (Nrf2) and HO-1 expression were lower in 3% DSS+ Ferr-1 group than 3% DSS group (P < 0.05). These data revealed that suppressing ferroptosis could effectively ameliorate DSS-induced UC involved in blocking Nrf2/HO-1 signaling pathway.

溃疡性结肠炎（UC）是一种炎症性疾病，其特征在于炎症反应不受控制。先前的研究表明，免疫功能障碍引起炎症介质的改变，而促肥大作用与活性氧（ROS）的致死性蓄积有关。因此，本研究旨在研究肥大症在硫酸葡聚糖硫酸钠（DSS）诱导的UC中的作用。建立了动物模型，并通过western blot检测了铁锈病的分子标记。结果表明，与对照组相比，3％DSS组COX2和ACSL4的表达显着增加，而GPX4和FTH1的水平降低（P<0.05）。同时，与3％DSS组相比，3％DSS + Ferrostatin-1组，3％DSS + liproxstatin-1组和3％DSS + Deferprone组的体重和结肠长度显着增加，并且炎症指标和MDA水平降低（P <0.05）。另外，在3％的DSS组中，COX2和ACSL4的mRNA和蛋白水平明显上调，而GPX4和FTH1的表达下调（P <0.05）。但是，在服用ferrostatin-1，liproxstatin-1（Lip-1）或deferprone（DFP）后，COX2，ACSL4，GPX4和FTH1的表达水平得到了证实。免疫组化分析显示，与3％DSS组相比，3％DSS + Ferr-1组COX2染色强度降低，GPX4染色强度升高（P<0.05）。此外，3％DSS + Ferr-1组的核因子类红细胞2相关2（Nrf2）和HO-1表达低于3％DSS组（P <0.05）。这些数据表明，抑制铁锈病可以有效改善DSS诱导的UC，参与阻断Nrf2 / HO-1信号通路。