Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice
Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice
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DOI：
10.1159/000513724
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发表时间：
2021-03-02
影响因子：
2.7
通讯作者：
Man, Mao-Qiang
中科院分区：
文献类型：
--
作者：
Wen, Si;Wu, Jiangmei;Man, Mao-Qiang
引言：全身或局部糖皮质激素（GC）可对皮肤结构和功能造成显著不良影响。虽然有些产品和成分可以改善GC诱导的表皮通透性屏障异常，但疗效中等。先前在正常小鼠中的研究表明，局部应用含类肝素的产品喜疗妥乳膏通过上调表皮增殖、表皮分化mRNA表达和脂质产生来改善表皮屏障功能。目的：本研究的目的是评估该产品的局部应用是否可以预防GC诱导的小鼠皮肤表皮功能变化。材料与方法：一组C57 BL/6 J小鼠用0.05%丙酸氯倍他索局部治疗，每日两次，持续6天，而另一组在每次应用丙酸氯倍他索后30分钟用喜疗妥乳膏局部治疗。未处理的小鼠作为正常对照。使用连接到MPA 5生理监测器的相应探针测量经表皮水分损失（TEWL）速率、角质层水合作用和皮肤表面pH。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。结果如下：与GC单独治疗相比，喜疗妥乳膏与GC联合应用可轻微但显著增加皮肤厚度（p < 0.05），同时真皮和表皮中PCNA mRNA表达水平增加。此外，喜疗妥乳膏还能显著抑制GC诱导的基础TEWL升高（p < 0.001）和屏障恢复延迟（p < 0.05），并能上调表皮外皮蛋白、HMGCoA和SPT 1的mRNA表达水平。然而，单独使用GC与GC +喜疗妥乳膏治疗的皮肤角质层水合作用和皮肤表面pH值相当。结论：局部应用含类肝素的产品可部分预防GC诱导的某些表皮功能的改变。
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 (R) 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 (R) 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 (R) 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 (R) 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 (R) cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.