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咪喹莫特诱导的瑞士 Wistar 大鼠皮肤病的分子和组织病理学特征:对新型抗银屑病治疗大鼠模型的贡献。

Molecular and histopathological profiling of imiquimod induced dermatosis in Swiss Wistar rats: contribution to the rat model for novel anti-psoriasis treatments.

机构信息

Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Zmaja od Bosne 8, 71000, Sarajevo, Bosnia and Herzegovina.

Veterinary Faculty, University of Sarajevo, Zmaja od Bosne 90, 71000, Sarajevo, Bosnia and Herzegovina.

出版信息

Mol Biol Rep. 2021 May;48(5):4295-4303. doi: 10.1007/s11033-021-06445-3. Epub 2021 Jun 7.

Abstract

Imiquimod (IMQ) induced human-like psoriasis in mice has been shown to be effective in testing and development of novel treatments. The IMQ psoriasis model has become widely used animal model, however, it is not completely characterized in different rat strains. We aimed to evaluate IMQ and betamethasone treatment for induction and reversal of psoriatic lesions on macroscopic, histological, genetic as well as cytokines and chemokines activation levels. Wistar rats were treated topically with IMQ. Adopted Psoriasis Area Severity Index (PASI) was calculated at the baseline, after the IMQ-symptoms induction and after betamethasone-symptoms reversal. Systematic effects were studied on cytokines and chemokines levels in plasma. Skin biopsy was taken to assess histological symptoms and selected inflammatory cytokines and receptors genes expression levels. Reversal of skin lesions, after betamethasone treatment, was significant (p = 0.03). Histological differences between untreated and IMQ-treated skin were significant for some markers (p < 0.05) though not significantly decreased by betamethasone treatment. Fourteen genes were significantly up-regulated after the IMQ and four genes were down-regulated after skin lesions reversal by betamethasone. This work provides new insights on biological effects of imiquimod induced psoriasis and its reversal by betamethasone treatment in Wistar rats. It also contributes to general knowledge of the rat model usage for testing of novel anti-psoriasis drugs.

摘要

咪喹莫特(IMQ)诱导的人类银屑病样小鼠已被证明在新型治疗药物的测试和开发中是有效的。IMQ 银屑病模型已被广泛应用于动物模型,但在不同大鼠品系中尚未完全得到描述。我们旨在评估咪喹莫特和倍他米松治疗对诱导和逆转银屑病病变的作用,从宏观、组织学、遗传以及细胞因子和趋化因子激活水平方面进行评价。Wistar 大鼠接受咪喹莫特的局部治疗。在基线、IMQ 症状诱导后和倍他米松症状逆转后,采用银屑病面积严重程度指数(PASI)进行评估。研究了细胞因子和趋化因子在血浆中的系统效应。进行皮肤活检以评估组织学症状和选择炎症细胞因子和受体基因的表达水平。与未经处理的皮肤相比,倍他米松治疗后的皮肤病变逆转具有显著差异(p=0.03)。尽管倍他米松治疗并不能显著降低,但未经处理和 IMQ 处理皮肤之间的一些标志物的组织学差异具有显著意义(p<0.05)。14 个基因在 IMQ 诱导后上调,4 个基因在倍他米松治疗后皮肤病变逆转时下调。这项工作提供了关于咪喹莫特诱导的银屑病及其在 Wistar 大鼠中被倍他米松治疗逆转的生物学效应的新见解。它也有助于增加对新型抗银屑病药物测试中大鼠模型使用的一般了解。

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