关键词: 银屑病； 二甲双胍； 疾病模型, 动物； 白细胞介素类； 肿瘤坏死因子α； 信号转导和转录激活因子3

Abstract: 【Abstract】 Objective To evaluate the effect of metformin on an imiquimod-induced psoriasis-like mouse model, and to explore its related mechanism. Methods A total of 50 male Balb/c mice were randomly divided into several groups: control group, imiquimod group （IM group） and imiquimod combined with metformin group （IM-Met group）. The IM-Met group were classified into 3 subgroups （100, 150 and 200 g/L IM-Met groups） according to the concentration of metformin. Mice in the control group were treated with topical vaseline cream on the back and intraperitoneal injection of 0.9% sodium chloride physiological solution of 0.3 millilitres every day. Mice in the IM group were treated with topical imiquimod cream on the back and intraperitoneal injection of 0.9% sodium chloride physiological solution of 0.3 millilitres every day. Mice in the 100, 150 or 200 g/L IM-Met groups were treated with topical imiquimod cream on the back and intraperitoneal injection of 100, 150 or 200 g/L metformin of 0.3 millilitres respectively every day. The changes of the erythema area, scales and psoriasis area and severity index （PASI） over time in each group were observed by naked eyes. These mice were sacrificed after 7 days of treatment. Western blot analysis was performed to determine the protein expression of interleukin （IL）-17 and phosphorylated signal transducer and activator of transcription 3 （p-Stat3） in the dorsal skin tissues of these mice, and enzyme-linked immunosorbent assay （ELISA） to detect serum levels of IL-17, IL-6 and tumor necrosis factor-α （TNF-α） in these mice. Comparison among these groups was carried out by using one-way analysis of variance, and means of two groups were compared by using least significant difference （LSD）-t test. Results Compared with the IM group, the 100, 150 and 200 g/L IM-Met groups showed alleviated erythema and scaling severity, and significantly decreased PASI score, protein expression of IL-17 and p-Stat3, and serum levels of inflammation factors such as IL-17, IL-6 and TNF-α （all P < 0.05）. Seven days later, the PASI score and protein expression of IL-17 and p-Stat3 were all significantly lower in the 150 g/L IM-Met group than in the 100 g/L IM-Met group （t = 4.18, -5.95, -2.80 respectively, P＜0.05, ≤ 0.01, ≤ 0.01 respectively）, but no significant differences were observed between the 150 g/L IM-Met group and 200 g/L IM-Met group（t = 0.29, -0.42, -0.32 respectively, P＞0.05, = 0.69, = 0.76 respectively）. The serum levels of IL-17, IL-6 and TNF-α in the 150 g/L IM-Met group were 33.388 ± 1.556 ng/L, 210.741 ± 4.440 ng/L and 249.434 ± 8.594 ng/L respectively, which were significantly higher than those in the 200 g/L IM-Met group （26.720 ± 2.156 ng/L, 174.997 ± 9.501 ng/L, 193.034 ± 6.661 ng/L respectively; t = 7.93, 10.79 and 16.403 respectively, all P＜0.05）, but significantly lower than those in the 100 g/L IM-Met group （44.008 ± 1.722 ng/L, 260.926 ± 7.724 ng/L, 271.409 ± 3.037 ng/L respectively; t = -14.47, -17.81 and -7.62 respectively, all P＜0.05）. Conclusion Metformin can alleviate psoriasis-like skin lesions and inflammation status in the imiquimod-induced psoriasis-like mouse model to a certain extent, which may be related to the decrease of p-Stat3 protein expression.

Key words: Psoriasis, Metformin, Disease models, animal, Interleukins, Tumor necrosis factor?alpha, Signal transducer and activator of transcription 3