本研究旨在探讨富马酸二甲酯（DMF）对氧化应激诱导的人表皮黑素细胞（MCs）损伤的保护作用及机制研究，从而为白癜风的临床治疗探索新的策略。

通过检测不同浓度DMF对MCs增殖活性的影响，筛选适宜的预处理浓度；利用过氧化氢（H₂O₂）处理MCs建立细胞氧化应激损伤模型；研究分为正常对照组、H₂O₂组（细胞模型）和H₂O₂+DMF组（药物预处理模型）。正置显微镜观察MCs形态并统计树突长度、树突数目；凋亡试剂盒评估DMF预处理对氧化应激状态下MCs凋亡的影响；流式细胞术及免疫荧光染色测定MCs内活性氧簇（ROS）水平，检测过氧化氢酶（CAT）及超氧化物歧化酶（SOD）活性；蛋白免疫印迹法检测核转录因子红系2相关因子（Nrf2）、p-Nrf2及下游靶基因血红素氧化酶-1（HO-1）表达水平。之后，将研究分为正常对照组、H₂O₂组、H₂O₂+DMF组及H₂O₂+DMF+ML385组（Nrf2抑制剂组），回复论证Nrf2蛋白在DMF抗氧化保护机制中的必要性。

与正常对照组相比，H₂O₂组树突长度缩短（P<0.01），树突数目减少（P<0.01），凋亡阳性细胞比例增加（P<0.01），细胞内ROS水平升高（P<0.01），SOD和CAT活性降低（P<0.001）。与H₂O₂组相比，H₂O₂+DMF组可显著抑制氧化应激诱导的MCs凋亡（P<0.05），同时降低胞内ROS的水平（P<0.05），提高SOD和CAT活性（P<0.01），增加Nrf2、p-Nrf2和HO-1的蛋白表达（P<0.05）。在回复论证实验中，加入Nrf2抑制剂预处理后，与H₂O₂+DMF组相比，H₂O₂+DMF+ML385组SOD和CAT活性显著降低（P<0.01），胞内ROS水平升高（P<0.05）。

DMF可提高MCs抗氧化酶活性，并激活Nrf2/HO-1信号通路，对氧化应激诱导的MCs损伤具有显著保护作用，有望通过抗氧化途径成为白癜风治疗的药物选择。

To explore how dimethyl fumarate (DMF) protects against oxidative stress-induced melanocyte injury, in order to offer new ideas for vitiligo treatment.

The optimal DMF concentration for melanocytes was determined by assessing its impact on their proliferation. An oxidative stress model was created using H₂O₂. The study involved four groups: normal control, H₂O₂-treated, H₂O₂+DMF, and H₂O₂+DMF+ML385 (a Nrf2 inhibitor). Melanocyte morphology, dendrite length, and cell number were observed. The effect of DMF on melanocyte apoptosis under oxidative stress was evaluated with an apoptosis detection kit. Flow cytometry and immunofluorescence staining were used to measure intracellular ROS levels and CAT/SOD activity. Western blot analysis was performed to detect the expression of Nrf2, p-Nrf2, and HO-1. The four groups were compared for the above parameters to confirm Nrf2's role in DMF's antioxidant mechanism.

The H₂O₂-treated group had shorter dendrites, fewer dendrites, more apoptosis-positive cells, higher intracellular ROS, and lower SOD/CAT activity than the normal control group. The H₂O₂+DMF group had significantly inhibited oxidative stress-induced melanocyte apoptosis, reduced ROS, increased SOD/CAT activity, and boosted Nrf2, p-Nrf2, and HO-1 expression. In the H₂O₂+DMF+ML385 group, SOD/CAT activity decreased, and intracellular ROS rose compared to the H₂O₂+DMF group.

DMF protects against oxidative stress-induced melanocyte injury by activating the Nrf2/HO-1 pathway and enhancing antioxidant capacity, showing potential for vitiligo therapy.