一种含肝素类产品的局部应用可减轻糖皮质激素诱导的小鼠表皮渗透性屏障的改变。

Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice.

机构信息

Dermatology Hospital of Southern Medical University, Guangzhou, China.

Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, China.

出版信息

Skin Pharmacol Physiol. 2021;34(2):86-93. doi: 10.1159/000513724. Epub 2021 Mar 2.

DOI:10.1159/000513724

PMID:33652434

Abstract

INTRODUCTION

Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production.

OBJECTIVE

The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin.

MATERIALS AND METHODS

One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes.

RESULTS

Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream.

CONCLUSION

Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

摘要

简介

全身性或局部性糖皮质激素（GCs）均可对皮肤结构和功能造成显著的不良反应。尽管某些产品和成分可改善 GC 引起的表皮渗透性屏障异常，但疗效中等。先前在正常小鼠中的研究表明，局部应用含有肝素样物质的制剂海肤康®乳膏可通过上调表皮增殖、表皮分化的 mRNA 表达和脂质产生来改善表皮屏障功能。

目的

本研究旨在评估该产品局部应用是否可预防 GC 诱导的小鼠皮肤表皮功能改变。

材料和方法

一组 C57BL/6J 小鼠每天两次用 0.05%丙酸氯倍他索局部治疗 6 天，另一组在每次应用丙酸氯倍他索后 30 分钟用海肤康®乳膏局部治疗。未处理的小鼠作为正常对照。使用分别与 MPA5 生理监测仪相连的探头测量经表皮水分丢失（TEWL）率、角质层水分含量和皮肤表面 pH 值。使用 qPCR 测量角质形成细胞分化相关蛋白和脂质合成酶的 mRNA 表达水平。

结果

与单独 GC 处理相比，GC 联合海肤康®乳膏应用可轻微但显著地增加皮肤厚度（p < 0.05），同时真皮和表皮中 PCNA 的 mRNA 表达水平也增加。此外，海肤康®乳膏可显著预防 GC 诱导的基础 TEWL 升高（p < 0.001）和屏障恢复延迟（p < 0.05），同时上调表皮内固醇硫酸酯酶和 SPT1 的 mRNA 表达水平。然而，单独应用 GC 与 GC+海肤康®乳膏处理的皮肤角质层水分含量和皮肤表面 pH 值相当。