外用紫草素对咪喹莫特诱导银屑病样小鼠模型的干预作用及对CEBPD表达的影响

目的:探讨外用紫草素对咪喹莫特诱导的银屑病样小鼠模型的干预作用及对CCAAT增强子结合蛋白δ（CEBPD）表达的影响。方法:将20只SPF级BALB/c雄性小鼠按照简单随机抽样法分为模型组、紫草素1组、紫草素2组及空白对照组，每组5只。模型组、紫草素1组和紫草素2组小鼠背部脱毛区均每日外涂5%咪喹莫特乳膏（IMQ）50...

Topical shikonin: intervention effect on an imiquimod-induced psoriasis-like mouse model and influence on CEBPD expression

【Abstract】 Objective To investigate the intervention effect of topical shikonin on an imiquimod-induced psoriasis-like mouse model and its effect on expression of CCAAT enhancer binding protein δ （CEBPD）. Methods Twenty specific pathogen-free BALB/c male mice were randomly and equally divided into model group, shikonin 1 group, shikonin 2 group and blank control group by using simple random sampling. Mice in the model group, shikonin 1 group and shikonin 2 group were topically treated with 50 mg of 5% imiquimod cream every day on the shaved back to establish the psoriasis-like mouse model. After 6-hour treatment, mice in the shikonin 1 group and shikonin 2 group were treated with 0.5 ml of shikonin at concentrations of 0.576 and 5.76 g/L respectively in the modeling area for 8 consecutive days; the blank control group received no treatment. Changes in the skin lesions of these mice were observed by naked eyes every day, and evaluated by using psoriasis area severity index （PASI）; after 8-day treatment, the mice were sacrificed by cervical dislocation, the dorsal skin tissues were resected, and immunohistochemical study and Western blot analysis were performed to determine the expression of CEBPD in the mouse epidermis. Statistical analysis was carried out with SPSS 16.0 software by using one-way analysis of variance for comparisons of observation indices among different groups, as well as least significant difference-t test for multiple comparisons. Results On day 8, the mice in the model group presented with obvious erythema, scales, and infiltrative and thickened skin lesions; compared with the model group, the skin lesions were markedly improved in the shikonin 1 group and shikonin 2 group, and the improvement was more obvious in the shikonin 2 group. On day 8, the PASI score significantly differed among the blank control group, model group, shikonin 1 group and shikonin 2 group （0, 11.0 ± 1.22, 8.6 ± 0.55, 5.8 ± 1.30 points, respectively; F = 128.21, P＜0.01）, and there were significant differences between any two groups （all P < 0.01）. Immunohistochemical study showed a significant difference in the expression of CEBPD （A value） among the model group, shikonin 1 group, shikonin 2 group and blank control group （0.072 ± 0.026, 0.177 ± 0.036, 0.290 ± 0.062, 0.407 ± 0.051, respectively; F = 48.895, P < 0.01）, and there were also significant differences between any two groups （all P < 0.01）. Western blot analysis showed that the CEBPD expression in the mouse epidermis was highest in the blank control group, followed in descending order by the shikonin 2 group, shikonin 1 group and model group, and significantly differed among the above 4 groups （F = 10.237, P＜0.05）; moreover, there were significant differences in the CEBPD expression between the model group and blank control group, as well as between the shikonin 1 group and blank control group （both P＜0.05）, while no significant difference was observed between the shikonin 2 group and the blank control group （P > 0.05）. Conclusion Topical shikonin could effectively interfere with the development of imiquimod-induced psoriasis-like mouse model; CEBPD expression decreased in the psoriasis-like mouse model, and could be markedly upregulated by topical application of shikonin.