Jiang Xue, Wu Xiaobin, Yang Fujin, Li Yanxi
Department of Dermatology, Chongqing Tranditional Chinese Medicine Hospital, Chongqing, China.
Department of Paediatrics, Chongqing Health Center for Women and Children, Chongqing, China.
Exp Dermatol. 2025 Apr;34(4):e70096. doi: 10.1111/exd.70096.
This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans-epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2-related cytokines (IL-5, IL-13, and IL-31) in skin lesions. Serum levels of IgE and thymus- and activation-regulated chemokine (TARC) were measured by enzyme-linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD-like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2-related cytokines (IL-5, IL-13, and IL-31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD-like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.
本研究旨在评估局部应用氟西汀在特应性皮炎（AD）样小鼠模型中的治疗效果及潜在机制。使用2,4 -二硝基氯苯（DNCB）建立AD样小鼠模型，并在皮肤损伤处局部应用氟西汀进行治疗。通过测量抓痕数量、皮肤厚度、经表皮水分流失（TEWL）和皮肤水分水平来评估治疗效果。通过苏木精和伊红染色以及甲苯胺蓝染色检查组织病理学变化，以评估局部炎症状态。采用定量聚合酶链反应（qPCR）测量皮肤损伤处Th2相关细胞因子（IL - 5、IL - 13和IL - 31）的表达。通过酶联免疫吸附测定（ELISA）测量血清中IgE和胸腺与活化调节趋化因子（TARC）的水平。局部应用氟西汀可显著减轻AD样小鼠的损伤症状，减少皮肤厚度和抓挠次数。该治疗增强了皮肤屏障的恢复，减少了炎症细胞尤其是肥大细胞的浸润。指示局部免疫状态的Th2相关细胞因子（IL - 5、IL - 13和IL - 31）水平也降低。血清中IgE和TARC的浓度呈下降趋势，TARC水平下降更为明显。我们的研究结果支持局部应用氟西汀在AD样小鼠模型中的治疗作用，其机制是通过修复皮肤屏障和抑制皮肤损伤处的Th2炎症反应，同时还能减轻瘙痒。这些结果表明氟西汀可能是AD的一种潜在治疗候选药物。
