皮肤性病诊疗学杂志2026，Vol.33Issue(8)：561-569,9.DOI:10.3969/j.issn.1674-8468.2026.08.001
4-辛基衣康酸通过抑制巨噬细胞铁死亡和氧化应激减轻小鼠特应性皮炎皮肤炎症损伤
4-Octyl itaconate attenuates inflammatory skin injury in a mouse model of atopic dermatitis by inhibiting macrophage ferroptosis and oxidative stress
摘要
Abstract
Objective To investigate whether macrophage ferroptosis occurs in atopic dermati-tis(AD)lesions and its role in AD,and to elucidate the mechanism by which 4-octyl itaconate(4-OI)alleviates AD inflammatory skin damage by inhibiting oxidative stress and macrophage fer-roptosis.Methods A total of 40 male C57BL/6 mice were used.Fifteen mice were randomly as-signed to 3 groups(n=5 each):the blank control group received no treatment,and the other two groups were treated with calcipotriol(MC903)to establish the AD model.Skin lesions were col-lected on days 0,7,and 14 post-modeling to observe histopathological changes,mRNA expression of IL-4,IL-5,and IL-13,and macrophage infiltration.Another 10 mice were randomly divided into sham and MC903-model groups(n=5 each).The sham group received topical ethanol,while the MC903-model group received topical MC903 for 14 consecutive days.The levels of oxi-dative stress,macrophage ferroptosis,and markers of the endogenous itaconate/Nrf2 pathway(Acod1,GPX4,PTGS2,Nrf2,and HO-1)in skin lesions were compared between the two groups.A further 15 mice were randomly divided into sham,MC903-model,and MC903+4-OI treatment groups(n=5 each).Mice in the MC903+4-OI group received intraperitoneal injection of 4-OI(50 mg/kg)concurrently with MC903 application for 14 consecutive days to evaluate the therapeutic effect of 4-OI on AD skin lesions.Histopathological changes were assessed by H&E staining.The expression levels of type 2 inflammatory cytokines(IL-4,IL-5,IL-13),ferroptosis-related markers,and GPX4,PTGS2,Nrf2,and HO-1 were detected by real-time quantitative PCR and Western blotting.Macrophage infiltration was examined by immunofluorescence.Oxida-tive stress was evaluated by ELISA for malondialdehyde(MDA)levels and by flow cytometry for DCFDA+macrophages in lesional skin.Results Over time following MC903 induction,the epi-dermis of lesional skin in the model group showed progressive thickening(P＜0.05),along with elevated levels of type 2 inflammatory cytokines IL-4,IL-5,and IL-13(P＜0.01)and increased macrophage infiltration.Compared with the sham group,the ferroptosis marker GPX4 was down-regulated and PTGS2 was abnormally upregulated(P＜0.01),while Acod1,Nrf2,and HO-1 were upregulated(P＜0.01).Concurrently,increased malondialdehyde(MDA)content and an elevated proportion of DCFDA+macrophages in lesional skin were observed(P＜0.01).In con-trast,treatment with 4-OI significantly ameliorated skin lesions(P＜0.01),reduced the levels of IL-4,IL-5,and IL-13(P＜0.01),suppressed macrophage ROS and MDA production,and re-versed the abnormal expression of GPX4 and PTGS2(P＜0.05)compared with the MC903 model group.Conclusions Macrophage ferroptosis is present in AD skin lesions,and 4-OI attenuates skin inflammatory damage by suppressing oxidative stress and macrophage ferroptosis.关键词
特应性皮炎/巨噬细胞铁死亡/4-辛基衣康酸/氧化应激Key words
atopic dermatitis/macrophage ferroptosis/4-octyl itaconate/oxidative stress引用本文复制引用
邓威威,钟泽敏,张悦,罗宇榕,谢安生,王迪..4-辛基衣康酸通过抑制巨噬细胞铁死亡和氧化应激减轻小鼠特应性皮炎皮肤炎症损伤[J].皮肤性病诊疗学杂志,2026,33(8):561-569,9.基金项目
国家自然科学基金(82404119) （82404119）
