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无角质层小鼠模型中 DHMEQ 与他克莫司软膏的抗特应性皮炎活性比较

Comparison of anti-atopic dermatitis activities between DHMEQ and tacrolimus ointments in mouse model without stratum corneum.

机构信息

School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.

Department of Research and Development, Shenzhen Wanhe Pharmaceutical Co., Ltd., Shenzhen 518057, China.

出版信息

Int Immunopharmacol. 2019 Jun;71:43-51. doi: 10.1016/j.intimp.2019.03.015. Epub 2019 Mar 13.

Abstract

This study is aimed to further investigate the anti-atopic dermatitis (AD) activities of dehydroxymethylepoxyquinomicin (DHMEQ) ointment and compare its effect with that of tacrolimus ointment based on the previous study that DHMEQ improves AD-like lesions. AD were induced by 2,4-dinitroclilorobenzene/oxazolone (DNCB/OX) repeatedly on the ears of BABL/C mice while medical tape was additionally used to disrupt stratum corneum in order to exacerbate the lesions. The mice were randomly divided into groups, which are normal, vehicle, DHMEQ (0.1%) and tacrolimus (0.1%). Those in the last two groups were externally applied with DHMEQ ointment and tacrolimus ointment, respectively. The results showed that both of them significantly improved dermatitis symptoms of DNCB/OX-induced AD-like lesions, such as redness, itching, weeping, scaling and thickening of the skin, while reducing epidermis thickness, dermis thickness and the number of mast cells as well, which were examined histopathologically. In contrast with DHMEQ, tacrolimus led to a significant decrease in body weight after long-term application. Both DHMEQ and tacrolimus suppress DNCB-induced increase of serum total IgE and attenuate expression of inflammatory factors IL-4, IL-6, IL-13, IL-1β and interferon (IFN)-γ in the disrupted ear tissues. On the other hand, the mice applied with tacrolimus became obviously irritable, jumping up and down, and inflammatory exudation on the lesioned-skin surface of the mice was remarkably observed. Contrary to the side effects made by tacrolimus, DHMEQ didn't cause any adverse stimulus response. As a conclusion, DHMEQ is safer, milder and more suitable for long-term use than tacrolimus for the treatment of AD-like lesions.

摘要

本研究旨在进一步探讨去甲氧基环氧青蒿素(DHMEQ)软膏的抗特应性皮炎(AD)活性,并基于先前研究中 DHMEQ 改善 AD 样病变的结果,比较其与他克莫司软膏的效果。AD 通过 2,4-二硝基氯苯/氧化苯乙烯(DNCB/OX)在 BABL/C 小鼠耳朵上反复诱导,同时使用医用胶带破坏角质层以加重病变。将小鼠随机分为正常组、对照组、DHMEQ(0.1%)组和他克莫司(0.1%)组。后两组分别给予 DHMEQ 软膏和他克莫司软膏外用。结果表明,两者均能显著改善 DNCB/OX 诱导的 AD 样病变的皮炎症状,如皮肤红肿、瘙痒、渗出、鳞屑和增厚,同时减少表皮厚度、真皮厚度和肥大细胞数量,经组织病理学检查证实。与 DHMEQ 相比,他克莫司长期应用后导致体重显著下降。DHMEQ 和他克莫司均能抑制 DNCB 诱导的血清总 IgE 增加,并减轻破坏耳组织中炎症因子 IL-4、IL-6、IL-13、IL-1β 和干扰素(IFN)-γ 的表达。另一方面,应用他克莫司的小鼠明显变得烦躁不安,上下跳跃,病变皮肤表面出现明显炎症渗出。与他克莫司的副作用相反,DHMEQ 不会引起任何不良反应。总之,DHMEQ 比他克莫司更安全、更温和、更适合长期用于治疗 AD 样病变。

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