紫外线照射对表皮通透屏障功能的影响及其意义

紫外线照射是影响皮肤生物功能最常见的因素之一.大部分皮肤鳞状细胞癌和基底细胞癌发生在曝光部位[1];皮肤弹性降低、皱纹增多也是常见的紫外线导致的损伤[2].皮肤色素增多、炎症形成及晒伤等也是与紫外线照射有关的皮肤病.此外,紫外线照射对表皮通透屏障功能也有不同程度的影响.然而,在防治紫外线照射对皮肤的损伤过程中,改善表皮通透屏障功能常常被忽略.为此,本文仅就紫外线照射对表皮通透屏障功能的影响及意义做一简述.     

表皮通透的屏障功能及其调节

保护机体、防止过多的水分丢失是皮肤的主要功能之一,角质层角质形成细胞及其细胞间脂类的组分对此功能起决定作用。角质形成细胞间的复层板层膜是皮肤屏障功能的主要结构。表皮通透的屏障功能影响皮肤的水分丢失量,且对表皮及真皮的生物活性(如角质形成细胞的增生、皮肤的炎症等)均有调节作用。诸多因素如脂类、性别、年龄、酸碱度、离子及精神等均可以作用于表皮通透的屏障功能。因此,深入地了解表皮通透的屏障功能及其影响因素有助于皮肤病的防治。     

皮肤屏障功能蛋白与银屑病的相关性研究进展

银屑病是一种常见的慢性炎症性皮肤病,容易复发,确切病因及发病机制并不完全清楚。各种表皮结构蛋白作为维持皮肤屏障功能的主要生化结构与银屑病发生发展密切相关。它们可以影响银屑病表皮的角质包膜形成、角蛋白纤维束形成、天然保湿因子生成、表皮水的转运,从而导致银屑病的皮肤屏障功能障碍。这些结构蛋白也是表皮角质形成细胞分化的重要标志,它们与银屑病角质细胞的过度增生和异常分化有着密切关联。表皮的结构蛋白异常被研究为导致银屑病皮肤屏障功能障碍的重要因素。本文主要对常见的表皮结构蛋白与银屑病的相关性研究进行综述。     

紫外线诱导的皮肤屏障功能损伤与葡萄籽原花青素的保护作用

狭义的皮肤屏障功能通常指表皮,尤其是角质层物理性或机械性屏障结构。但是从组织细胞学角度来看,皮肤的物理性屏障功能不仅仅依赖于表皮角质层,而是依赖于表皮的全层结构。广义的皮肤屏障功能不仅包括其物理性屏障作用,还包括皮肤的色素、神经、免疫屏障作用及其他与皮肤功能相关的诸多方面。本文就紫外线及葡萄籽提取物原花青素对皮肤屏障功能影响进行总结,探讨葡萄籽提取物原花青素是否具有抵抗紫外线所致的皮肤屏障功能损伤、延缓皮肤光老化的作用。     

评估表皮通透屏障功能的方法及其应用

表皮通透屏障功能是指表皮防止物质通过表皮进出机体的功能.该功能对于表皮的增生分化、炎症的形成与发展以及抗微生物感染等方面都具有重要作用.而表皮通透屏障功能受体内外多种生物、物理因素的影响.因此,调节表皮通透屏障功能是皮肤保健和防治某些皮肤病的重要手段;评估表皮通透屏障功能是了解皮肤生物功能以及判断皮肤保健、治疗效果的方法.评估表皮通透屏障功能的方法很多.除测量透皮失水率外,超微示踪、透皮微昔分析、同位素及荧光标记定位和定量等都是评估表皮通透屏障功能的有效方法.了解这些方法的特点对于选择恰当的手段和有效地评估表皮通透屏障功能具有重要的指导意义.     

不同年龄人群曝光部位皮肤claudin1蛋白表达及其与经皮水分丢失的关联

目的:观察不同年龄阶段健康人群曝光皮肤组织中紧密连接蛋白claudin1分子的表达情况,探讨其与表皮屏障功能之间的关联性,并分析慢性紫外线照射对皮肤组织中claudin1蛋白的表达及表皮屏障功能的影响。方法:收集不同年龄共39人曝光部位皮肤组织(包括颈项部、手背部或额面部),其中20岁组9例,20~50岁组14例,50岁组16例。分别以RT-PCR检测皮肤组织中的claudin1分子转录情况,以免疫组化法检测claudin1蛋白的表达,并检测不同皮肤组织的经皮水分丢失(TEWL)值。结果:RT-PCR检测显示cluadin1分子的转录水平均随年龄增大而下调,50岁组claudin1分子的mRNA表达较20岁组明显降低(P=0.0370)。免疫组化结果显示曝光部位皮肤组织中claudin1蛋白的表达强度随年龄增长而减弱,与年龄呈负相关,与RT-PCR结果一致。老年组(50岁组)曝光部位皮肤的TEWL值较中年组(20~50岁组)及青年组(20岁组)均升高,TEWL值与claudin1蛋白的表达呈负相关(P=0.0475)。结论:慢性紫外线照射可引发人曝光部位皮肤的屏障功能损伤,而这种屏障功能受损可能与claudin1蛋白的下调表达有关。     

改善表皮通透屏障功能对特应性皮炎的防治作用

表皮通透屏障是皮肤的防御功能之一,它不仅影响物质透过皮肤进出机体以及微生物的侵入,对皮肤的其他生物功能也具有重要的调节作用［１］。表皮通透屏障功能降低是一些皮肤病（包括特应性皮炎和银屑病）发病的主要因素之一［2］。改善表皮通透屏障功能有助于防治这些皮肤病,已成为防治特应性皮炎的手段之一。由于改善表皮通透屏障功能的制剂或有效活性成分不同,其对皮肤功能的影响也不同。因此,在临床上选择改善表皮通透屏障功能的制剂时,应综合考虑皮肤的生物物理特性和不同制剂的特性,使其发挥最大的疗效。在此,仅综述几种主要改善表皮通透屏障功能的制剂对特应性皮炎的防治作用……     

表皮细胞紧密连接在银屑病发病机制中的作用

表皮细胞紧密连接被认为是控制表皮通透性屏障功能的"主要控制因子"。新近研究表明,表皮细胞紧密连接功能障碍参与银屑病的发病,紧密连接蛋白的表达和定位异常是银屑病表皮细胞异常增殖分化的上游影响因素。表皮紧密连接功能障碍与慢性炎症相互促进,形成恶性循环,维持银屑病皮损区的炎症反应。通过调节紧密连接蛋白的表达及组装,提高皮肤屏障功能,为银屑病等与屏障相关疾病的治疗提供了新的策略。     

敏感性皮肤及其处理对策

敏感性皮肤是指皮肤对多种内外因素的耐受性降低、敏感性增强。敏感皮肤的发生与年龄、性别、身体解剖部位以及种族有关。敏感性皮肤者生活质量下降。由于其病因不明,有效控制敏感性皮肤一直是个挑战。近来研究显示,表皮通透屏障功能和瞬时感受器电位香草酸受体与敏感性皮肤的发生有关。因此,改善表皮通透屏障功能和瞬时感受器电位香草酸受体抑制剂可能有助于改善敏感性皮肤。     

皮肤屏障中的脂质

皮肤被覆于人体表面,在保护体内组织免受外界有害因素的损伤中发挥重要的屏障功能。皮肤脂质作为皮肤的重要组分,主要分布于水脂膜、表皮和皮下脂肪层,在皮肤屏障中具有十分重要的作用。皮肤脂质成分、结构以及含量的改变都会影响皮肤的屏障功能,严重时还会导致多种疾病的发生。因此皮肤脂质在皮肤屏障中的作用越来越受到重视。     

老年表皮功能与老年炎症

【摘要】 目前研究认为，老年病包括心血管疾病、2型糖尿病以及阿尔茨海默症等的发生与衰老相关的慢性炎症（“炎症性衰老”）有关，但是炎症的来源一直未知。有研究显示，老年表皮功能异常可能是老年炎症的根源。与年轻人相比，老年人表皮功能的变化包括角质层含水量降低、皮肤表面pH值升高以及表皮通透屏障功能恢复速度减慢，这些改变均能导致皮肤炎症。瘙痒症好发于老年人，瘙痒引起的搔抓可进一步破坏表皮通透屏障功能和诱发炎症。皮肤持续轻微的炎症有可能导致系统炎症。在老年小鼠和老年人的研究均证明，改善表皮功能可以降低循环血炎症细胞因子表达量，提示老年表皮功能异常可能是老年炎症的根源，改善表皮功能可能有助于预防和缓解老年病。     

【开放获取】皮肤干燥是通透屏障功能受损的表现吗？

【摘要】 有学者认为,皮肤干燥是表皮通透屏障功能受损的表现,但目前尚没有足够的证据证明这一观点。实际上,皮肤干燥是角质层含水量降低的表现。角质层含水量主要由角质层天然保湿因子的量决定,而表皮通透屏障功能则主要由角质层脂质的质和量以及结构蛋白决定。如果皮肤干燥是由表皮通透屏障功能降低所致,那么,角质层含水量应当与透皮失水率呈负相关性。但是研究表明,无论是正常人皮肤、鱼鳞病皮损或皮脂腺缺乏的小鼠皮肤,角质层含水量与透皮失水率均无负相关性。相反,有研究显示,人角质层含水量与透皮失水率呈正相关性。因此,皮肤干燥似乎不是表皮通透屏障功能受损的表现。     

Impact of ultraviolet radiation and ozone on the transepidermal water loss as a function of skin temperature in hairless mice

Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.     

Wie die Sonne unsere Haut altern l?sst

Extrinsic factors (= environmentally induced skin aging) lead to both epidermal and dermal changes. Recent investigations have shown that the dermis plays the decisive role, at least for skin aging caused by ultraviolet (UV) radiation. Exposure to UV radiation results in an accumulation of damage to the mitochondrial DNA of dermal fibroblasts and thus an altered gene expression of the affected cells, which chronically drives both the dermal (e.g., wrinkle formation) and epidermal (atrophy, barrier dysfunction) aging process. This knowledge is currently being used to develop highly effective cosmetic strategies to reverse the skin aging process.     

Increased 1-Deoxysphingolipids and Skin Barrier Dysfunction in the Skin of X-ray or Ultraviolet B Irradiation and Atopic Dermatitis Lesion Could Be Prevented by Moisturizer with Physiological Lipid Mixture

BackgroundSkin diseases characterized by epithelial barrier dysfunction show altered sphingolipid metabolism, which results in changes in the stratum corneum intercellular lipid components and structure. Under pathological conditions, 1-deoxysphingolipids form as atypical sphingolipids from de novo sphingolipid biosynthesis.ObjectiveThis study investigated the potential role of 1-deoxysphingolipids in skin barrier dysfunction secondary to X-ray and ultraviolet B (UVB) irradiation in vitro and in vivo. It was also evaluated changes in the expression of 1-deoxysphingolipids in lesional human skin of atopic dermatitis.MethodsIn this study, the changes in these 1-deoxysphingolipids levels of skin and serum samples were investigated in skin barrier dysfunction associated with X-ray and UVB irradiation in vitro and in vivo.ResultsIncreased 1-deoxysphingolipids were observed in cultured normal human epidermal keratinocytes after X-ray irradiation. X-ray or UVB irradiation increased the production of 1-deoxysphingosine in a reconstituted 3-dimensional (3D) skin model. Interestingly, treatment with a physiological lipid mixture (multi-lamellar emulsion contained pseudoceramide), which can strengthen the epidermal permeability barrier function, resulted in decreased 1-deoxysphingosine formation in a reconstituted 3D skin model. Further investigation using a hairless mouse model showed similar preventive effects of physiological lipid mixture against 1-deoxysphingosine formation after X-ray irradiation. An increased level of 1-dexoysphingosine in the stratum corneum was also observed in lesional skin of atopic dermatitis.Conclusion1-deoxysphingosine might be a novel biomarker of skin barrier dysfunction and a physiological lipid mixture treatment could prevent 1-deoxysphingosine production and consequent skin barrier dysfunction.     

Barrière épidermique

The skin acts as an interface between the body and its surrounding environment. The epidermis, the surface layer of the skin, is chiefly responsible for this interactive protective function. The epidermal barrier may be subdivided into three defensive systems: the photoprotective barrier, the immune barrier, and the physical and chemical barrier of the stratum corneum or horny layer. To protect against harmful ultraviolet radiation, the epidermis has absorption factors such as melanin, produced by melanocytes, and urocanic acid, which is a degradation product of filaggrin. The epidermal immune defence system comprises an innate component, which is rapid but non-specific, together with adaptive response, which is systemic and antigen-specific, initiated by Langerhans cells. The stratum corneum, derived from terminal differentiation of epidermal keratinocytes, plays a key role as a physical and chemical permeability barrier. This horny layer is made up of corneocytes, covered with horny envelopes and linked to one another by corneodesmosomes and by extracellular matrix sheets. The epidermal barrier, which is constantly being renewed, is characterised by its extremely great capacity of adaptation to changing conditions in the environment.     

Epidermal barrier function and systemic diseases

The skin is a vital organ for life and, among its many functions, the role as a protective barrier is one of the most important. It is the main boundary between the body and the external environment. As defensive barrier, the epidermis protects internal organs from physical and chemical trauma, microorganism invasion, and ultraviolet radiation. It also acts in the regulation of transepidermal movement of water and electrolytes, and in preventing dehydration, all of which are essential for sustaining life. The main role is allotted to the stratum corneum and to the lipid matrix located in the intercellular space. The occurrence of dysfunction in the epidermal barrier is an important factor in the physiopathogenesis of skin diseases, particularly atopic dermatitis and psoriasis. There are few, but important, systemic changes that influence or are influenced by dysfunctions in the epidermal barrier. We review the effects of some systemic diseases on the maintenance of the skin's homeostasis.     

1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Topical application of emollients prevents dry skin-inducible intraepidermal nerve growth in acetone-treated mice

In common dermatoses, such as atopic dermatitis (AD), a decline in skin barrier function often accompanies an increased severity of clinical symptomatology, including pruritus [1]. Skin barrier disruption alters epidermal innervation and increases nerve density in the skin [2]. These findings are indicative of increases in sensory receptors responsive to exogenous trigger factors, suggesting that hyperinnervation is partly responsible for intense itch sensations [2]. Therefore, the abnormal innervation associated with skin barrier dysfunction such as dry skin has been considered as a target of antipruritic therapy. Moreover, recent studies have demonstrated that epidermal innervation is probably regulated by a fine balance of nerve elongation factors (e.g., nerve growth factor (NGF), amphiregulin, gelatinase) [2] and nerve repulsion factors (e.g., semaphorin 3A (Sema3A), anosmin-1) [2] and [3]. Although many people use emollients daily to alleviate symptoms of clinically and subjectively dry skin [4], the effects of emollients on nerve fiber density and nerve growth activity in dry skin remain unclear. We therefore examined the anti-nerve growth effects of petrolatum and heparinoid cream in the epidermis of acetone-treated mice, an animal model of acute dry skin [5].     

What's new in dermatological research?

Dermatological research has been very active this year. Most of the numerous fields investigated involve the mechanisms of cutaneous regeneration and barrier function. A novel target of early ultraviolet-induced skin photodamage, the Syk kinase, has been recently identified. Synergistic relationship between telomere damage and cutaneous progerin production during cell senescence may also participate in the natural skin aging process. Interestingly, ultraviolet radiation induces an inhibitory effect on subcutaneous lipogenesis. Androgenetic alopecia or common baldness is not characterized by loss of hair follicle stem cells but by a defect in the conversion of hair follicle stem cells into active progenitor cells. It has been shown that the cornified envelope functions not only as a physicomechanical barrier, but also as both a biochemical line of antoxidant defense and an immunological line of defense. Like human papillomaviruses, Merckel cell polyomavirus belongs to the skin microbiome and different studies have demonstrated the protective role of epidermal resident microflora through the activation of innate immunity. Production of antimicrobial peptides and the activation of inflammasome and plasmacytoid dendritic cells are involved in the modulation of the cutaneous barrier function. Results from different studies suggest that IL-22 and IL-36 may be common mediators of both innate and adaptive immune responses. All these pathways interact not only to maintain cutaneous homeostasis and integrity (wound healing) but also to regulate autoinflammatory and autoimmune dermatoses (psoriasis, lupus, rosacea, atopic dermatitis, etc...). In addition, molecular mechanisms that regulate T helper type 2 differentiation and the retention at the site of inflammation of Th2 cells have been identified. New promising therapeutic targets for different chronic dermatosis are thus suggested. Mechanobiology and mechanotransduction are also emerging fields that investigate mechanical interactions between living cells and their environment and the conversion of mechanical cues into biochemical signals. Electronic second skin is now a current concept through bio-integrated epidermal electronics platforms used for different monitoring and stimulations of body functions.