角蛋白17反义寡核苷酸对银屑病SCID小鼠模型的作用

目的 建立重症联合免疫缺陷(SCID)小鼠银屑病动物模型,观察角蛋白17(K17)反义寡核苷酸(ASODN)对银屑病动物模型的作用.方法 将斑块状银屑病患者的皮损移植于SCID小鼠,构建银屑病SCID小鼠模型.然后分别以脂质体介导的K17 ASODN、正义寡核苷酸(SODN)及单纯乳剂基质作用于皮损,大体及H-E染色观察皮损改变,RT-PCR以及免疫组化检测K17的变化.结果 成功构建了SCID小鼠银屑病动物模型:与SODN组及单纯乳剂基质对照组相比,K17 ASODN治疗组皮损炎症恢复明显加快,组织学评分显著降低(P<0.01),K17 mRNA水平以及蛋白表达水平也均有不同程度降低.结论 K17 ASODN能够显著改善SCID鼠移植模型的银屑病病理改变,有望成为一种新的治疗措施.

Effects of keratin 17 antisense oligonucleotide on psoriasis in a SCID-hu xenogeneic transplantation model

Objective To investigate the effects of keratin 17(K17)antisense oligonucleotide (ASODN)on psoriasis using a SCID-hu xenogeneic transplantation model.Methods Psoriatic lesions were obtained from patients with plaque psoriasis and grafted onto the skin of SCID mice to develop the SCID-hu xenogeneic transplantation model.Totally,12 SCID mice were divided into three groups,and lipo- somal emulsions containing K17 ASODN,K17 SODN and vehicle alone were applied topically to grafts in the individual groups,respectively.The changes of grafts were observed macrographically as well as histopathogically with HE staining.The expression of K17 mRNA and protein was detected in the three groups by RT-PCR and immunohistochemistry,respectively.Results The grafts maintained all the charac- teristics of psoriasis after transplantation,and animal model of psoriasis was established successfully.The grafts' inflammation was recovered more rapidly,and histological score reduced significantly in ASODN group than those in SODN and control groups.Also,the expression of K17 mRNA and protein was decreased signifi- cantly in ASODN group than that in other two groups as shown by RT-PCR and immunohistochemistry. Conclusions K17 ASODN could markedly relieve the pathological changes of psoriatic gratis in SCID-hu xenogeneic transplantation model,and is expected to be a new approach to the treatment of psoriasis.