关键词: 银屑病, 疾病模型, 动物, 干扰素α, 白细胞介素2, 肿瘤坏死因子α, 白细胞介素23, 咪喹莫特

Abstract: 【Abstract】 Objective To investigate the feasibility of construction of rat models of psoriasis-like lesions by using interleukin （IL）-23/ T-helper 17 （Th17） axis-related cytokines combined with imiquimod. Methods A total of 110 Wistar rats were randomly divided into normal control group, imiquimod alone group, imiquimod combined with interferon （IFN）-α2a （180 000, 60 000, 20 000 IU/kg） groups, imiquimod combined with tumor necrosis factor （TNF）-α （45 000, 15 000, 5 000 IU/kg） groups, and imiquimod combined with IL-2 （90 000, 30 000, 10 000 IU/kg） groups, and there were 10 rats in each group. After hair removal from the central area （2 cm × 2 cm） of the rat back, rats in the imiquimod alone group were topically treated with imiquimod 5% cream at a dose of 20 mg/cm2 on the shaved back; rats in the imiquimod combined with different cytokine groups were treated with topical imiquimod 5% cream at the same dose on the shaved back for 15 minutes followed by intraperitoneal injections of cytokines at corresponding doses once a day for 10 consecutive days. During the treatment, skin lesions on the rat back were evaluated by using the psoriasis area and severity index （PASI） scores every day. On day 10, serum samples were collected from the rats after anesthesia, and enzyme-linked immunosorbent assay （ELISA） was performed to detect levels of IL-17A, TNF-α, IL-23, IFN-α and IL-1β in the serum samples in each group; then, the rats were sacrificed, lesional skin tissues on the rat back were taken for histopathological examinations and evaluated by Baker scores; an immunohistochemical study was conducted to determine the expression of CD4 and CD8 in some skin lesions. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference （LSD）-t test for multiple comparisons; for data with heterogeneous variance, the Kruskal-Wallis H test was used. Results On day 3 after molding, the rats in the imiquimod alone group and combination groups gradually presented with psoriasis-like skin manifestations, such as erythema, scales and epidermal thickening; the PASI scores reached a peak on day 7 in the imiquimod alone group, and on day 6 in the combination groups. On day 10, histopathological examination of the skin lesions in the imiquimod alone group and combination groups both showed different psoriasis-like pathological features, such as hyperkeratosis, parakeratosis, acanthosis, thinning or disappearance of the granular layer. There were significant differences in the PASI scores and Baker scores among the normal control group, imiquimod alone group and combination groups （H = 43.33, F = 42.15, both P < 0.001）. The PASI scores were higher in the imiquimod combined with IFN-α2a （180 000 IU/kg） group and the imiquimod combined with IL-2 （90 000 IU/kg） group （9.4 ± 1.1, 8.8 ± 0.6, respectively） than in the imiquimod alone group （7.5 ± 1.1, P = 0.002, 0.030 respectively）; the Baker scores were higher in the imiquimod combined with IFN-α2a （180 000, 60 000 IU/kg） groups, the imiquimod combined with TNF-α （45 000 IU/kg） group, and the imiquimod combined with IL-2 （90 000 IU/kg） group than in the imiquimod alone group （all P < 0.05）. The serum levels of TNF-α, IL-17A, IL-1 β and IL-23 significantly differed among groups （F = 128.97, F = 6.90, H = 27.45, H = 21.10, all P < 0.05）. Compared with the imiquimod alone group, the IL-17A level significantly increased in the imiquimod combined with IL-2 （30 000 IU/kg） group （5.54 ± 1.78 pg/ml vs. 4.20 ± 1.14 pg/ml, P = 0.009）, and the IL-23 level significantly increased in the imiquimod combined with IL-2 （90 000 IU/kg） group （37.89 ± 32.85 pg/ml vs. 8.56 ± 6.08 pg/ml, P = 0.036）. Immunohistochemical study showed significant differences in the expression of CD4 and CD8 in skin lesions among all groups （F = 7.21, H = 18.32, both P < 0.001）, and the expression of CD4 and CD8 in skin lesions was significantly higher in the imiquimod combined with IL-2 （90 000 IU/kg） group than in the imiquimod alone group （t = -2.46, -2.32, respectively, both P < 0.05）. Conclusion Imiquimod combined with IFN-α2a or IL-2 could promote the occurrence of psoriasis-like skin lesions in rats, aggravate the development of psoriasis and prolong the maintenance time of the rat models.

Key words: Psoriasis, Disease models, animal, Interferon-alpha, Interleukin-2, Tumor necrosis factor-alpha, Interleukin-23, Imiquimod