神经酰胺在人皮肤中的主要功能

皮肤中神经酰胺主要位于表皮,是表皮中的主要脂质,具有保湿、信号转导、免疫调节等功能。其含量的变化可能导致皮肤屏障功能受损,甚至一些皮肤疾病的发生,如特应性皮炎、银屑病等。本文对皮肤中神经酰胺的主要作用进行综述。     

皮肤角质层神经酰胺的检测方法

神经酰胺即N-脂酰基(神经)鞘氨醇,是人体角质层脂质的重要成分,皮肤中的神经酰胺在人表皮角质层结构稳定、细胞增殖和分化、表皮屏障损伤修复中起重要作用,其性质和数量影响着皮肤屏障及部分皮肤病,目前检测神经酰胺的方法种类较多,但只有小部分可运用于皮肤角质层神经酰胺的检测。本文简单综述现有的皮肤角质层神经酰胺的检测方法。     

神经酰胺信号转导与角朊细胞的增殖分化

神经酰胺是表皮角层中主要的脂质成分,与皮肤的屏障功能有密切关系。近年来发现神经酰胺还可作为重要的第二信使,参与角朊细胞的增殖、分化及凋亡等过程。     

神经酰胺与特应性皮炎相关性研究进展

特应性皮炎（ atopic dermatitis,AD）的发病机制尚不清楚,可能与遗传因素、免疫因素、皮肤屏障功能障碍、精神因素及生活习惯与环境因素相关。然而有研究显示,AD发病的首要机制可能是皮肤屏障功能障碍,特别是脂质中神经酰胺含量的减少是皮肤屏障功能受损的主要原因之一［1］。神经酰胺在维持皮肤屏障功能方面有重要作用,因此关于神经酰胺与AD的相关性研究,对分析不同严重程度AD患者的皮肤状态、指导临床用药有重要意义……     

神经酰胺信号转号与角朊细胞的增殖分化

神经酰胺是表皮角层中主要的脂质成分，与皮肤的屏障功能有密切关系，近年来发现神经酰胺还可作为重要的第二信使，参与角朊细胞的增殖，分化及凋亡等过程。     

神经酰胺代谢途径对皮肤屏障功能影响研究进展

神经酰胺是角质层脂质的主要成分,是反映皮肤屏障功能的关键性物质,其含量的变化会使细胞间脂质结构发生变化,导致皮肤屏障功能障碍,而引发相关皮肤病。本文对神经酰胺的合成、分解、对皮肤屏障功能的影响及相关皮肤病进行综述。     

神经酰胺及其相关皮肤病

神经酰胺是角质层细胞间脂质的主要组成成分.神经酰胺在调节皮肤的生物活性及表皮的生理功能中起重要作用.在人类皮肤角质层中,根据其鞘氨脂碱基基团和碳氢化合物链长不同,已发现的神经酰胺可分为9种.许多伴皮肤屏障功能异常的皮肤病如特应性皮炎和银屑病,其表皮神经酰胺的含量异常,外用适当比例的神经酰胺制剂可缓解其病变.外用具有生理活性的细胞间脂质可能是治疗皮肤病的新途径.     

神经酰胺在特应性皮炎皮肤屏障功能中的研究进展

皮肤屏障功能障碍在特应性皮炎(AD)的发病机制中具有重要作用。在遗传和环境因素相互作用下,皮肤的屏障功能降低,其保持皮肤水分、维持正常生理功能的作用受到影响,出现皮肤干燥、脱屑等表现,引发或加重AD。神经酰胺是皮肤屏障细胞间脂质的主要成分,其代谢异常可使皮肤屏障出现障碍,外用含神经酰胺润肤剂可以显著改善AD患儿皮肤屏障功能,为恢复AD皮肤屏障功能提供了一种新方法。     

保湿剂对成人轻度特应性皮炎皮肤角质层神经酰胺含量的影响

目的研究保湿剂对成人轻度特应性皮炎治疗前后皮肤角质层神经酰胺含量及含水量的变化。方法本实验选取25例成人轻度特应性皮炎患者和10例健康对照者进行研究,特应性皮炎患者外用保湿剂治疗;采用胶带剥离法采集实验组和对照组前臂屈侧皮肤角质层样本,用高效液相色谱–质谱法联用定量检测角质层神经酰胺3含量,用SOFT 5.5皮肤性质测试仪测定皮肤含水量;分析治疗前后患者皮肤神经酰胺3含量及含水量的变化,并根据EASI评分法评价疗效。结果实验组皮肤角质层神经酰胺3含量(0.89±0.49)ng/mg、含水量(31.97±12.04)均低于健康对照组[(10.22±2.69)ng/mg和(67.81±11.05)],两组差异有统计学意义(P0.05);实验组治疗4周后皮肤角质层神经酰胺3含量(2.28±0.69)ng/mg和含水量(50.54±17.22)均高于治疗前,差异有统计学意义(P0.05);EASI评分治疗后(0.73±0.66)较治疗前(2.37±1.50)下降,差异有统计学意义(P0.05);皮肤含水量与角质层神经酰胺3含量呈正相关关系(r=0.51,P0.05),与EASI评分呈负相关关系(r=-0.49,P0.05)。结论成人轻度特应性皮炎患者皮肤角质层神经酰胺3含量下降,使用保湿剂辅助治疗能促进患者症状减轻。     

神经酰胺与皮肤屏障

神经酰胺是人体角质层脂质的主要成分,在皮肤的合成和分布有一定的规律。其质和量的变化可以导致脂质结构的改变,从而影响皮肤屏障功能。不同亚型神经酰胺作用不同,在角质形成细胞增殖、分化及凋亡中起重要作用,是皮肤屏障损伤修复后期重要的效应物质。许多皮肤病可导致角质层屏障功能的破坏,而屏障功能的破坏又是一些皮肤病的病因或加重因素。故神经酰胺在皮肤中的作用越来越受重视。     

Efficacy of the combined use of a facial cleanser and moisturizers for the care of mild acne patients with sensitive skin

Acne is a common skin disease that involves the seborrheic area of the face and results from the obstruction of hair follicles followed by inflammation. Careful face washing helps to improve and prevent acne; however, intensive washing has a risk of inducing skin barrier impairment and dry skin, especially in sensitive skin. We hypothesized that skin care combining mild skin cleansing and intensive moisturizing (“combination skin care”) may be effective in the care of acne in subjects with dry skin and/or sensitive skin. We developed a combination skin care with a weakly acidic foaming facial skin cleanser based on a mild detergent, an aqueous lotion with eucalyptus extract and a moisturizing gel containing pseudo‐ceramide and eucalyptus extract. To optimize an ideal facial skin care system for mild acne on sensitive skin, we performed a 4‐week clinical trial with 29 post‐adolescent Japanese women with mild acne with dry and sensitive skin. The acne significantly decreased after this trial accompanied by the improvement of dry skin, a significantly increased endogenous ceramide level in the stratum corneum and an elongated alkyl chain length of the non‐hydroxy acyl sphingosine type ceramide. No adverse events due to the test samples were observed. Based on diagnosis by a dermatologist, 97% of the subjects found the combination skin care to be “useful” or “slightly useful”. Based on these findings, the combined use of a facial skin cleanser and moisturizers is safe and effective for the care of acne in post‐adolescent Japanese women with sensitive skin.     

Effects of a ceramide‐containing water‐in‐oil ointment on skin barrier function and allergen penetration in an IL‐31 treated 3D model of the disrupted skin barrier

Atopic dermatitis (AD) is a chronically relapsing, pruritic inflammation of the skin with dryness and disturbed skin barrier function. Recently, we established that IL‐31 treatment of human 3D skin models resulted in a disrupted skin barrier phenotype resembling AD. In this model, we found that IL‐31 interferes with the differentiation of keratinocytes and inhibits the expression of terminal differentiation markers. In the present study, we investigated the effects of a ceramide‐containing water‐in‐oil skin care ointment on the physical skin barrier structure and function in disrupted skin barrier models, generated either by using primary normal human epidermal keratinocytes (NHEK) or HaCaT cells. We observed that the physical skin barrier of the models recovered after daily topical treatment with the ceramide‐containing ointment. Topical application of the ointment prevented downregulation of filaggrin and disorganization of other differentiation markers, such as keratin 10 and β4‐integrin, as demonstrated by immunohistological analysis. The expression of Ki67 was also upregulated in response to the ointment. Furthermore, functional studies revealed that local application of the ointment diminished the increased uptake of fluorescently labelled recombinant allergens of timothy grass (phl p1) in our model. In conclusion, our data revealed that topical application of a ceramide‐containing skin care ointment reduced IL‐31 induced impairments of the physical skin barrier and skin barrier function in an in vitro model of the disrupted skin barrier. This standardized model can be utilized in the future to monitor ex vivo effects of various topical therapies on skin morphology, physiology, and gene expression.     

Dietary sphingolipids improve skin barrier functions via the upregulation of ceramide synthases in the epidermis

Sphingolipids are ubiquitous in eukaryotic organisms and are significant components in foods. It has been reported that treatment with sphingolipids prevents colon cancer, improves skin barrier function and suppresses inflammatory responses. However, the mechanisms for those effects of dietary sphingolipids are not well understood. In this study, to investigate the effects of dietary glucosylceramide (GluCer) and sphingomyelin (SM) on skin function, we characterized the recovery of skin barrier function and the change in sphingolipid metabolism‐related enzymes in the epidermis using a special Mg‐deficient diet–induced atopic dermatitis‐like skin and tape‐stripping damaged skin murine models. Our results show that dietary GluCer and SM accelerate the recoveries of damaged skin barrier functions. Correspondingly, dietary sphingolipids significantly upregulated the expression of ceramide synthases 3 and 4 in the epidermis of the atopic dermatitis‐like skin model (P < 0.05). In the case of cultured cells, the expression of ceramide synthases 2‐4 in normal human foreskin keratinocytes was significantly upregulated by treatment with 0.001–0.1 μm sphingoid bases (sphinganine, sphingosine and trans‐4,cis‐8‐sphingadienine) (P < 0.05). These results suggest that the effects of dietary sphingolipids might be due to the activation of ceramide synthesis in the skin, rather than the direct reutilization of dietary sphingolipids. Our findings provide a novel insight into the mechanisms of the skin barrier improving effect and a more comprehensive understanding of dietary sphingolipids.     

Incorporation of ceramide 3B in dermatocosmetic emulsions: effect on the transepidermal water loss of sodium lauryl sulphate-damaged skin

BACKGROUND: In previous work we reported on the efficacy of cosmetic body lotions enriched with skin-identical lipids to reduce the transepidermal water loss (TEWL) of ageing and sodium lauryl sulphate (SLS)-damaged skin. The observations made depended on the experimental design and clearly raised the question of the importance of the galenic formulation of skin ceramide-containing products. OBJECTIVES: The aim of the present work was to study the different galenic forms in which ceramide 3B (0.2% w/v) can be incorporated into common o/w emulsions. In addition, we investigated whether supplementation of skin care products with ceramide 3B enriched with penetration enhancers and coemulsifiers could exert a beneficial effect on barrier function, done by measuring their effects on the TEWL of SLS-induced scaly skin. RESULTS: We found that the technique of incorporating ceramide 3B into the o/w emulsions was important for their final stability. However, no additional positive effect on the TEWL values of SLS-damaged skin could be observed when the efficacy of the ceramide-containing emulsions was compared with that of proper controls. CONCLUSIONS: Although suitable galenic formulas were developed, no positive effect on TEWL could be observed when ceramide 3B was added in a final concentration of 0.2% (w/v) to different o/w emulsions and applied to SLS-damaged skin.     

pH in nature,humans and skin

The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1–5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium‐hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia). Later on, it was found that the pH influences skin barrier function, lipid synthesis and aggregation, epidermal differentiation and desquamation. Enzymes of ceramide metabolism (e.g. β‐glucocerebrosidase or acid sphingomyelinase) as well as proteases (e.g. chymotryptic enzyme or cathepsin D linked to epidermal differentiation and desquamation) are regulated by the pH. Experimental disruption of the physical barrier leads to an increase of pH, returning to normal levels only after many hours. Inflammatory skin diseases and diseases with an involvement of the epidermis exhibit a disturbed skin barrier and an increased pH. This is known for atopic dermatitis, irritant contact dermatitis, ichthyosis, rosacea and acne, but also for aged and dry skin. Normalizing the pH by acidification through topical treatment helps to establish a physiological microbiota, to repair skin barrier, to induce epidermal differentiation and to reduce inflammation.     

Ceramide analogue 14S24 selectively recovers perturbed human skin barrier

BACKGROUND: Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis. OBJECTIVES: To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model. METHODS: Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L). RESULTS: Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin. CONCLUSIONS: Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.     

皮肤屏障功能与其神经鞘酯类关系的探讨

利用新生大鼠皮肤的培养，研究皮肤屏障功能与其神经鞘酯类的关系．结果发现皮肤屏障功能在培养后的第１天略有降低，以后恢复正常．第１０天起明显下降；皮肤的神经鞘酯类化合物随着培养时间的延长，乙酰神经酰胺，乙酰葡萄糖神经酰胺趋向降低，糖鞘酯呈显著下降，神经既胺趋向增高。结果提示皮肤屏障功能与神经鞘酯类的代谢有一定关系。     

Keratinocyte differentiation and upregulation of ceramide synthesis induced by an oat lipid extract via the activation of PPAR pathways

Activation of peroxisome proliferator‐activated receptors (PPARs) has been shown to have an important role in skin barrier function by regulating differentiation and lipid synthesis in keratinocytes. Oat (Avena sativa) has long been used as a soothing agent to relieve skin irritations, and the clinical benefits of topical oat formulations have been proven; however, the mechanistic understanding of oat's mode of action remains unknown. We investigated whether an oat lipid extract could activate PPARs and subsequently increase epidermal lipid synthesis and differentiation markers. Primary human epidermal keratinocytes and transformed cell lines were treated with PPAR agonists and oat lipid extracts to investigate the PPAR agonism. PPAR target genes and epidermal differentiation markers were analysed using quantitative real‐time PCR and HPTLC analysis. Oat lipid extract demonstrated robust dual agonism for PPARα and PPARβ/δ, and increased direct PPAR target gene induction in primary human keratinocytes. In addition, oat oil treatment increased both receptor expression and, consistent with the literature on PPARs, oat oil treatment resulted in a significant upregulation of differentiation genes (involucrin, SPRRs and transglutaminase 1) and ceramide processing genes (β‐glucocerebrosidase, sphingomyelinases 3 and ABCA12). Further, oat oil treatment in keratinocytes significantly increased ceramide levels (70%), suggesting a functional translation of PPAR activation by oat oil in keratinocytes. Taken together, these results demonstrate that oat lipids possess robust dual agonistic activities for PPARα and PPARβ/δ, increase their gene expression and induce differentiation and ceramide synthesis in keratinocytes, which can collectively improve skin barrier function.