关键词: 皮炎, 特应性, 小鼠, 近交BALB C, 青藤碱, 治疗, 白细胞介素1β, 白细胞介素6, 免疫球蛋白E, p38丝裂原活化蛋白激酶类, 核因子κB

Abstract: 【Abstract】 Objective To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis （AD）-like mouse models. Methods Thirty female BALB/c mice （6 - 8 weeks old） were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene （DNCB） on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg?1·d?1 （100 μl per dose, twice daily） . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin （IL）-1β, IL-6, and immunoglobulin E （IgE） were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase （MAPK） and nuclear factor （NF）-κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups （all P < 0.05）. Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues （all P < 0.01）. Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues （all P < 0.05）. Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores （both P < 0.05）. Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group （both P < 0.05）. Conclusion Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Key words: Dermatitis, atopic, Mice, inbred BALB C, Sinomenine, Therapy, Interleukin-1beta, Interleukin-6, Immunoglobulin E, p38 Mitogen-activated protein kinases, NF-kappa B