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评估局部奥卡西替尼和指甲修剪作为实验小鼠溃疡性皮肤病的治疗方法。

Evaluation of topical oclacitinib and nail trimming as a treatment for murine ulcerative dermatitis in laboratory mice.

机构信息

Comparative Medicine Research Unit, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.

Department of Neurosurgery, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.

出版信息

PLoS One. 2022 Oct 18;17(10):e0276333. doi: 10.1371/journal.pone.0276333. eCollection 2022.

Abstract

Murine ulcerative dermatitis (UD) is a common, multifactorial skin disease of C57BL/6 and C57BL/6-background strains of mice. Many treatment options have been previously reported but have been variably successful and may interfere with specific research studies. Janus kinase (JAK) inhibitors, such as oclacitinib, have been used to treat allergic dermatitis in humans, dogs, and other species. Additionally, topical oclacitinib was shown to improve an induced model of dermatitis in mice. We hypothesized that topical application of oclacitinib in conjunction with hind limb nail trimming would improve UD lesion scores more than our institutional standard treatment regime using meloxicam, topical antibiotic ointment, and nail trimming or nail trimming alone. To test this, mice with naturally occurring UD were recruited to the study and assigned to one of three treatment groups (n = 14/group): nail trim only; nail trim plus meloxicam and topical triple antibiotic ointment; or nail trim plus topical oclacitinib. UD was assessed on days 1, 7, and 14 for all treatment groups, and scored based on a previously published scoring system that quantitatively scored UD lesions based on pruritus, character of the lesion, size of lesion, and location of lesion. Here we found that mean UD scores decreased from day 1 to day 7 and from day 1 to day 14 for all treatment groups. However, there was no significant difference in mean UD score between the treatment groups at any timepoint. These data show that topical oclacitinib and nail trimming together improved UD lesion scores comparably to our institutional standard treatment and nail trimming alone. However, further studies may be warranted to investigate other potential applications of oclacitinib to treat UD.

摘要

实验性小鼠溃疡性皮肤病(UD)是 C57BL/6 及其近交系小鼠常见的多因素皮肤疾病。先前已有多种治疗方案报道,但疗效不一,且可能会干扰特定的研究。Janus 激酶(JAK)抑制剂,如奥卡替尼,已被用于治疗人类、犬类和其他物种的过敏性皮炎。此外,局部奥卡替尼已被证明可改善诱导的小鼠皮炎模型。我们假设局部应用奥卡替尼联合后肢趾甲修剪可改善 UD 病变评分,优于我们机构使用美洛昔康、局部抗生素软膏和趾甲修剪或单独修剪趾甲的标准治疗方案。为了验证这一点,招募了患有自然发生 UD 的小鼠参与研究,并将其分为三组治疗(每组 n = 14):仅修剪趾甲;修剪趾甲加美洛昔康和局部三联抗生素软膏;或修剪趾甲加局部奥卡替尼。所有治疗组均在第 1、7 和 14 天评估 UD,并根据先前发表的评分系统进行评分,该系统根据瘙痒、病变特征、病变大小和病变位置对 UD 病变进行定量评分。结果发现,所有治疗组的 UD 评分均从第 1 天到第 7 天和从第 1 天到第 14 天下降。然而,在任何时间点,治疗组之间的 UD 评分均无显著差异。这些数据表明,局部奥卡替尼和修剪趾甲联合应用可改善 UD 病变评分,与我们机构的标准治疗和单独修剪趾甲相当。然而,可能需要进一步研究以探讨奥卡替尼治疗 UD 的其他潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3194/9578627/ed12fe9dac3a/pone.0276333.g001.jpg

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