卡泊三醇对咪喹莫特诱导的小鼠银屑病模型的影响

Effect of calcipotriol on imiquimod (IMQ)-induced psoriasis-like mouse model

目的:探讨卡泊三醇对咪喹莫特诱导的小鼠银屑病模型的治疗作用及机制。方法:BALB/c小鼠随机分为3组:空白对照组、咪喹莫特组和卡泊三醇组。咪喹莫特组小鼠背部每日涂抹5%咪喹莫特乳膏,卡泊三醇组小鼠背部每日先涂抹5%咪喹莫特乳膏,6 h后再涂抹卡泊三醇搽剂,空白对照组每日涂抹凡士林作为对照。采用银屑病皮损面积与严重度指数(PASI)评分观察各组小鼠皮损变化情况;光镜观察皮损组织形态学变化;免疫病理分析各组皮损组织中淋巴细胞、中性粒细胞和树突状细胞浸润情况;实时荧光定量聚合酶链反应(q-PCR)对小鼠皮损组织中炎性细胞因子白细胞介素(IL)-17和干扰素(IFN)-γ的表达水平进行检测。结果:与咪喹莫特组比较,卡泊三醇组银屑病样皮损变化显著减轻,临床症状评分(clinical score,CS)降低,差异有统计学意义(P<0.05);与咪喹莫特组比较,卡泊三醇组表皮厚度明显变薄,银屑病病理评分(Baker)明显降低,差异有统计学意义(P<0.05);免疫病理结果显示卡泊三醇组皮损中的淋巴细胞、中性粒细胞和树突状细胞均低于咪喹莫特组,卡泊三醇组IL-17和IFN-γ表达水平与咪喹莫特组比较,差异均有统计学意义(P<0.05)。结论:卡泊三醇具有一定的抗银屑病作用;该作用可能与降低皮损处的IL-17和IFN-γ表达水平有关。

Objective： To investigate the therapeutic effect and mechanisms of calcipotriol on imiquimod（IMQ）-induced pso- riasis-like mouse model. Methods： BALB/c mice were randomly divided into three groups： control group, IMQ and calcipotri- ol groups. Mice in both IMQ and calcipotriol groups were treated topically with 5% imiquimod cream daily while mice in calcipotriol group were also treated with topical calcipotriol 6 hr after application of imiquimod cream. Mice treated with vase- line served as controls. After 7-day treatments, psoriasis area and severity index was used to evaluate the psoriasis severity. H＆E staining and immunohistochemical staining of CD3, CDllc and myeloperoxidase（MPO） were used to assess morphologi- cal changes and cutaneous inflammation. Expression levels of mRNA for IL-17 and IFN-γ were assessed using real-time quantitative PCR. Results： Calcipotriol significantly alleviated psoriasis severity in the IMQ-treated mice. The scores of clini- cal symptoms were significantly lower in calcipotriol group versus imiquimod group（P〈0.05）. Moreover, both average epidermal thickness and the Baker scores were lower in calcipotriol group versus imiquimod group （P〈0.05）. Immunohistochemistry showed that calcipotriol markedly reduced the cellular infiltration of T cells, CD11c-DCs and neutrophils in dermis in com- parison with IMQ group. Calcipotriol decreased the expression levels of mRNA for IL-17 and INF-γ（P〈0.05）. Conclusion： Anti-psoriatic effects of calcipotriol may be through down regulation of IL-17 and IFN-γ expression.