关键词: 银屑病, 维甲酸, 他扎罗汀, 紫外线疗法, 基质金属蛋白酶13

Abstract: 【Abstract】 Objective To determine the expression of matrix metalloproteinase 13 （MMP13） in patients with psoriasis, and to evaluate the effect of tazarotene and narrow-band ultraviolet B （NB-UVB） on the expression of MMP13 in mice with psoriasis-like dermatitis. Methods Lesional skin tissues and normal skin tissues were collected from 18 patients with psoriasis vulgaris and 10 healthy controls respectively, who were enrolled from General Hospital of Tianjin Medical University between May 2019 and August 2019, and serum samples were collected from all the subjects. A total of 25 specific pathogen-free （SPF） male BALB/c mice were randomly divided into control group, imiquimod group, imiquimod + NB-UVB group, imiquimod + tazarotene group and imiquimod + tazarotene + NB-UVB group. The control group received topical vaseline cream on the back once every morning; imiquimod group and imiquimod + NB-UVB group received imiquimod cream on the back once every morning; imiquimod + tazarotene group and imiquimod + tazarotene + NB-UVB group received imiquimod cream on the back once every morning, and tazarotene cream on the back once at night; imiquimod + NB-UVB group and imiquimod + tazarotene + NB-UVB group received NB-UVB irradiation on the back every other day at noon, with the dose being 300 mJ/cm2 in the first session and increasing by 50 mJ/cm2 in every session. The modeling lasted 7 days. After successful modeling, blood samples were obtained from the eyeballs of the mice, and skin tissues were resected from the back of the mice after being sacrificed by cervical dislocation on day 8. Changes in the epidermal thickness and pathological manifestations were observed by hematoxylin and eosin （HE） staining, protein expression of MMP13 in skin tissues was determined by immunohistochemical study, and the serum level of MMP13 was detected by enzyme-linked immunosorbent assay. Comparisons between 2 groups were performed by using two-independent-sample t test, comparisons among several groups by using one-way analysis of variance, multiple comparisons by using least significant difference-t test, and comparisons of enumeration data by using chi-square test. Results The skin lesions of the patients with psoriasis were strongly positive for MMP13, and the MMP13 expression levels in the epidermis and serum （84.11 ± 17.16, 13.29 ± 3.95 μg/L, respectively） were significantly higher in the patients with psoriasis than in the healthy controls （11.98 ± 4.08, 7.46 ± 1.58 μg/L, respectively, both P < 0.01）. Compared with the control group （1.26 ± 0.04 μm, 25.40 ± 2.34, 185.76 ± 7.22 μg/L, respectively）, a significant increase was observed in the epidermis thickness（7.93 ± 0.59 μm, P < 0.01）, as well as MMP13 levels in the epidermis and serum in the imiquimod group （147.14 ± 5.53, 215.98 ± 15.17 μg/L, respectively, both P < 0.01）. Compared with the imiquimod group, the imiquimod + tazarotene group, imiquimod + NB-UVB group, and imiquimod + tazarotene + NB-UVB group all showed significantly decreased epidermal thickness （3.56 ± 0.37 μm, 3.83 ± 0.39 μm, 2.14 ± 0.34 μm, respectively, all P < 0.05）, MMP13 levels in the epidermis （120.42 ± 3.23, 91.08 ± 0.46, 71.12 ± 7.11, respectively, all P < 0.05） and serum （197.39 ± 3.92 μg/L, 196.13 ± 11.76 μg/L, 183.21 ± 14.99 μg/L, respectively, all P < 0.05）. Conclusions MMP13 protein expression markedly increased in the skin lesions and sera of patients with psoriasis, and decreased in skin lesions and sera of mice with psoriasis-like dermatitis after the treatment with tazarotene and NB-UVB. MMP13 may be involved in the development of psoriasis, and tazarotene and NB-UVB may inhibit the development of psoriasis by reducing the expression of MMP13.

Key words: Psoriasis, Tretinoin, Tazarotene, Ultraviolet therapy, Matrix metalloproteinase 13