咪喹莫特联合干扰素-α诱导大鼠银屑病模型的建立

Establishment of the Psoriasis Rats Models Induced by Imiquimod Combined with Interferon-α

目的用咪喹莫特联合干扰素(IFN)-α诱导大鼠银屑病模型。方法将Wistar大鼠随机分为空白对照组、咪喹莫特单用组、咪喹莫特联用IFN-α组及PA-J组。每日上午,咪喹莫特单用组大鼠背部涂抹5%咪喹莫特乳膏;咪喹莫特联用组及PA-J组大鼠背部涂抹5%咪喹莫特乳膏,10 min后将重组人干扰素α-2a注射液按照1万U/500 g腹腔注射;空白对照组大鼠背部涂以等量凡士林。下午,PA-J组大鼠背部按0.5 mg/只滴涂药物,连续10 d。第11 d对大鼠背部皮损进行银屑病皮损面积和严重程度指数(PASI)评分;取皮损部分进行组织病理学观察并进行Baker评分;免疫组化法检测皮损中白细胞介素(IL)-17表达情况。结果咪喹莫特联用组大鼠皮肤可见大块鳞屑、红斑;病理观察可见颗粒层变薄甚至消失、棘层肥厚、乳突上顶,真皮层大量炎性细胞浸润等特点;皮损组织中IL-17表达明显增高(P<0.01)。与单用组比较,联用组PASI评分及Baker评分明显增加(P<0.05,0.01)。与联用组比较,PA-J能明显改善皮损症状,降低PASI、Baker评分及IL-17表达(P<0.05,0.01)。结论咪喹莫特联合IFN-α诱导银屑病大鼠模型有典型的银屑病临床及病理特点,可作为银屑病研究的动物模型。

Objective Psoriasis rats models induced by imiquimod combined with interferon(IFN)-α.Methods Wistar rats were randomly divided into blank control group,imiquimod monotherapy group,imiquimod combined with IFN-αgroup and PA-J group.Rats in the imiquimod monotherapy group were treated with 5%imiquimod cream;rats in the imiquimod combination group and PA-J group were treated with 5%imiquimod cream and recombinant human IFN-α-2a injection was intraperitoneally injected at 10,000 U/500 g after ten minutes every morning.The rats in the blank control group were coated with the same amount of vaseline.In the afternoon,rats in the PA-J group were dosed with drug 0.5 mg each for ten consecutive days.On the 11th day,psoriasis area and severity index(PASI)score was performed on the dorsal skin lesions of rats.The lesions were taken for histopathological observation and Baker score.The expression of interleukin(IL)-17 in the lesions was detected by immunohistochemistry.Results The skin of the imiquimod combination group showed large scales and erythema;pathological observation showed that the granular layer became thinner or even disappeared,the acanthosis was thick,the mastoid top was over,and the inflammatory layer infiltrated in the dermis.The expression of IL-17 was significantly increased in lesions(P<0.01).Compared with imiquimod monotherapy group,the PASI and Baker score of the imiquimod combination group increased significantly(P<0.05,0.01).Compared with imiquimod combination group,PA-J can significantly improve skin symptoms and reduce PASI scores,Baker scores and the expression of IL-17(P<0.05,0.01). Conclusion Imiquimod combined with IFN-α induced psoriasis rats models have typical clinical and pathological features of psoriasis,it can be used as an animal model for psoriasis research.