Methodological refinement of Aldara-induced psoriasiform dermatitis model in mice
Methodological refinement of Aldara-induced psoriasiform dermatitis model in mice
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DOI：
10.1038/s41598-019-39903-x
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发表时间：
2019-03-06
影响因子：
4.6
通讯作者：
Kemeny, Agnes
中科院分区：
文献类型：
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作者：
Horvath, Szabina;Komlodi, Rita;Kemeny, Agnes
咪喹莫特（IMQ）诱导的皮肤炎症是目前最广泛接受的银屑病动物模型，然而，它具有一些局限性。我们已经修改了IMQ模型，以尽量减少其对有效地保持特征性皮肤反应的全身效应。原始方案（OP）使用62.5 mg Aldara乳膏（或凡士林）涂抹小鼠剃毛背部皮肤4天。相比之下，在我们的改良方案（MP）中，将25 mg Aldara和凡士林同时应用于小鼠背部皮肤上的单独Finn室中。在OP和MP组中，组织学显示明确的银屑病样皮炎特征。此外，皮肤剥脱和血液灌注值相似。虽然Aldara在MP组中引起皮肤厚度显著增加，但仅在OP组中观察到显著体重减轻、脾脏肿大、血浆中炎性细胞因子水平升高和给药相关死亡。我们的新方法重现了银屑病皮肤变化，突出显示大大减少了全身炎症反应。在同一只小鼠上具有银屑病样和对照皮肤区域也减少了个体间差异。此外，新方法允许长期IMQ治疗研究，以模拟银屑病的慢性性质。最后，我们的实验方法也可用于其他小鼠模型，以防止局部应用药物的不良全身效应。
Imiquimod (IMQ)-induced skin inflammation is currently the most widely accepted psoriasis animal model, however, it features several limitations. We have modified the IMQ-model to minimize its systemic effects towards effectively maintaining the characteristic skin reactions. The original protocol (OP) uses 62.5 mg Aldara cream (or vaseline) on the shaved back skin of mice for 4 days. In contrast, in our modified protocol (MP) 25 mg Aldara and vaseline are applied simultaneously in separate Finn chambers over the dorsal skin of mice. In both the OP and MP groups, histology showed unequivocal hallmarks of psoriasiform dermatitis. Additionally, skin scaling and blood perfusion values were similar. While Aldara elicited significantly increased skin thickness in the MP group, significant weight loss, spleen enlargement, increased inflammatory cytokine levels in plasma, and treatment related death were only observed in the OP group. Our new method reproduces psoriatic skin alterations highlighting considerably reduced systemic inflammatory reactions. Possessing psoriasiform and control skin areas on the same mouse also reduces inter-individual differences. Additionally, the new method permits prolonged IMQ treatment studies to mimic the chronic nature of psoriasis. Finally, our experimental approach may also be used in other mouse models, to prevent the undesired systemic effects of topically applied drugs.