5种常用药物对咪喹莫特诱导小鼠银屑病样皮损模型形成的影响  

Effect of Psoriasis Orientated Drugs on Psoriasis-like Mice Model Induced by Imiquimod

作　　者：赵京霞[1] 底婷婷[1] 王燕[1] 刘欣[1] 梁代英[1] 李萍[1] 

机构地区：[1]北京市中医研究所,北京100010

出　　处：《中国皮肤性病学杂志》2014年第3期234-238,259,共6页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金资助项目(No.81072810)

摘　　要：目的探讨5种治疗银屑病的常用药物对咪喹莫特诱导的银屑病样模型皮损形成的影响。方法 Balb/c雄性小鼠,随机分为正常对照组、模型组、阿维A组、地塞米松组、甲氨蝶呤组、雷公藤多苷组、环孢素组。采用银屑病皮损面积和疾病严重程度(PASI)评分标准观察银屑病样小鼠模型皮损变化情况。光镜下观察皮损组织形态学变化、测量表皮层厚度;免疫组织化学法检测增殖细胞核抗原(PCNA)反映表皮角质形成细胞增殖程度;检测皮损中CD3反映T淋巴细胞浸润程度。结果阿维A组、地塞米松组、甲氨蝶呤组、雷公藤多苷组小鼠皮损与同期模型组相比,皮损症状明显改善,各项指标PASI评分都低于同期模型组小鼠。环孢素对该模型皮损的形成呈现一个先抑制后促进的作用。环孢素组PASI积分高峰出现的时间比模型组晚2～3d。HE染色显示:与模型组小鼠比较,阿维A组、地塞米松组、甲氨蝶呤组、雷公藤多苷组小鼠皮肤表皮层较平整,角化不全的细胞明显减少,表皮层厚度明显低于模型组。而环孢素组与模型组小鼠皮损组织学表现相似,表皮层厚度与模型组相比差异无统计学意义(P>0.05)。免疫组织化学染色显示:阿维A组、地塞米松组、甲氨蝶呤组、雷公藤多苷组皮损组织中PCNA及CD3表达均显著低于模型组,差异有统计学意义(P<0.01或<0.05)。环孢素组与模型组相比差异无统计学意义(P>0.05)。结论临床治疗银屑病药物阿维A、地塞米松、甲氨蝶呤、雷公藤多苷可有效干预咪喹莫特诱导的小鼠银屑病样皮损的形成,以上药物对银屑病样皮损的表皮细胞增殖及T淋巴细胞浸润均有抑制作用,因此该模型可作为进行研究银屑病药物研究的药理模型。但环孢素A对由咪喹莫特诱导的银屑病样小鼠模型的反应不敏感。Objective To observe the effects of psoriasis therapeutic options on psoriasis-like lesions induced by Imi- quimod in mice. Methods Balb/c mice were randomly divided into seven groups ： control, model, Acitretin （ Aci ）, Dexamethasone （ Dex ） , Methotrexate （ MTX ） , Triptergium wilfordii （ GTW ） , and Cyclosporine A （ CysA）. The morphological changes of lesional skin in mice were evaluated according to the psoriasis area and severity index（PASI） and HE staining. Proliferating cell nuclear antigen（PCNA） and C D3 expression were investigated by immunohistochemical staining. Results Compared with model group, the psoriasis-like le- sions of Aci-, Dex-, MTX-, GTW-treated groups were alleviated, with decreased PASI scores, epidermal parak- eratosis and reduced PCNA, CD3 expression. The morphological changes and PCNA, CD3 expression in CysA group has not shown significant difference. Conclusion The drugs for psoriasis treatment in clinic such as Aci, Dex, MTX and GTW could improve imiquimod-induced murine psoriasis-like lesions probably by inhibi- ting keratinocytes over-proliferation, parakeratosis, and T lymphocyte infiltration. However, we did not find the inhibition effect of CysA on the formation of imiquimod-induced psoriasis-like lesions in mice.

关 键 词：银屑病 咪喹莫特 阿维A 地塞米松 甲氨蝶呤 雷公藤多苷 环孢素 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]