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

发布时间：2018-11-08 16:22

【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(P0.05)。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(P0.01或0.05)。环孢素组与模型组相比差异无统计学意义(P0.05)。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。
[Abstract]:Objective to investigate the effects of five common drugs for psoriasis on the formation of psoriasis-like model induced by Imiquimod. Methods Balb/c male mice were randomly divided into normal control group, model group, avea group, dexamethasone group, methotrexate group, tripterygium wilfordii polyglycoside group and cyclosporine group. The area of psoriatic lesions and the severity of psoriasis were measured by (PASI) score. Histomorphologic changes were observed under light microscope and the thickness of epidermis was measured. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry to reflect the degree of proliferation of epidermal keratinocytes and CD3 was detected to reflect the degree of infiltration of T lymphocytes in skin lesions. Results the skin lesions of Avera group, dexamethasone group, methotrexate group and Tripterygium wilfordii polyglycoside group were significantly improved compared with the model group, and the PASI scores of each indexes were lower than those of the model group. Cyclosporine showed a first inhibition and then a promotion effect on the formation of skin lesions in the model. The peak time of PASI score in cyclosporine group was longer than that in model group. Compared with model group, the skin epidermis of Avera group, dexamethasone group, methotrexate group and tripterygium wilfordii polyglycoside group was more smooth than that of model group. The cells with hypokeratosis decreased significantly, and the thickness of epidermis was significantly lower than that of the model group. However, the skin lesions in the cyclosporine group and the model group were similar, and the thickness of the epidermis was not significantly different from that in the model group (P0.05). Immunohistochemical staining showed that the expressions of PCNA and CD3 in the lesions of Avera group, dexamethasone group, methotrexate group and tripterygium wilfordii group were significantly lower than those in the model group (P0.01 or 0.05). There was no significant difference between the cyclosporine group and the model group (P0.05). Conclusion Avera, dexamethasone, methotrexate, tripterygium wilfordii polyglycosides can effectively interfere with the formation of psoriatic lesions induced by Imiquimod in mice. The above drugs can inhibit the proliferation of epidermal cells and the infiltration of T lymphocytes in psoriatic lesions, so this model can be used as a pharmacological model for the study of psoriasis drugs. But cyclosporine A was insensitive to the model of psoriasis induced by Imiquimod.
【作者单位】：北京市中医研究所;
【基金】：国家自然科学基金资助项目(No.81072810)
【分类号】：R758.63

【参考文献】