关键词: 皮炎, 特应性, 疾病模型, 动物, 炎症, 皮肤表现, 细胞因子类, 微生物群落, 酸化脂肪酸酯, 16S rRNA, 葡萄球菌属

Abstract: 【Abstract】 Objective To investigate the efficacy of acidified aliphatic ester in the treatment of atopic dermatitis （AD） in mouse models, and to preliminarily explore its mechanisms of action. Methods Twenty female BALB/c mice aged 6 to 8 weeks were randomly divided into 2 groups: 5 mice in the blank control group were topically treated with absolute ethanol on both ears （14.3 μl per ear） every day, and 15 mice in the model group were topically treated with calcipotriol liniment （14.3 μl per ear） and 20 g/L ovalbumin （25 μl per ear） on both ears every day for 10 consecutive days to establish AD-like mouse models. From day 11, 15 mice in the model group were randomly divided into 3 groups （5 mice in each group）, including AD model group, aliphatic ester group, and acidified aliphatic ester group; in the forenoon, all the 3 groups continued to be topically treated with calcipotriol liniment and ovalbumin to maintain AD-like models; in the afternoon, the aliphatic ester group and acidified aliphatic ester group were topically treated with aliphatic ester and acidified aliphatic ester respectively （10 μl per ear）, and no treatment was given to the AD model group. Changes in body weight, ear thickness, ear skin lesion scores, and scratching frequency were observed. Ear skin swabs were obtained from the mice on days 10 and 14 for 16S rRNA gene - based microbial diversity tests. On day 14, mice were sacrificed after reflectance confocal microscopy examinations of the ear skin, ear tissues were resected for hematoxylin and eosin staining, mast cell staining, and real-time fluorescence-based quantitative PCR （RT-qPCR）, and blood samples were collected for detection of serum IgE levels. One-way analysis of variance was used for analysis of data that met homogeneity of variance criteria, and least significant difference-t test for multiple comparisons. Results On day 14, the severity of mouse ear lesions was the highest in the AD model group, followed in turn by the aliphatic ester group, acidified aliphatic ester group, and blank control group; compared with the AD model group, the acidified aliphatic ester group showed significantly decreased mouse ear thickness （F = 897.50, P < 0.001）, skin lesion scores （F = 268.80, P < 0.001）, scratching frequency （F = 64.36, P < 0.001）, and epidermal thickness （F = 256.20, P < 0.001）. In addition, RT-qPCR indicated that the expression of inflammatory factors such as interleukin （IL）-33, thymic stromal lymphopoietin, IL-4, and tumor necrosis factor-α in lesional areas, and the degree of mast-cell infiltration were all significantly lower in the acidified aliphatic ester group than in the AD model group （F = 3.38, 8.70, 41.73, 44.30, 134.30, P = 0.049, = 0.001, < 0.001, < 0.001, ＜0.001, respectively）. Microbial diversity tests showed that the acidified aliphatic ester treatment could inhibit the colonization of Staphylococcus spp. in the ears of AD-like mouse models, and the Shannon index and Simpson index significantly differed among the 4 groups （F = 9.00, 7.92, P = 0.001, 0.002, respectively）. Conclusion Acidified aliphatic ester could improve skin lesions of AD-like mouse models, possibly by regulating immunity, suppressing inflammation, and restoring skin microecological diversity.

Key words: Dermatitis, atopic, Disease models, animal, Inflammation, Skin manifestations, Cytokines, Microbial consortia, Acidified aliphatic ester, 16S rRNA, Staphylococcus