表皮通透屏障功能对皮肤的调节作用及意义

表皮通透屏障功能除调节水分经表皮进出机体外,还对皮肤的其他生物功能如炎症、表皮增生、pH及离子的分布等也具有重要地调节作用。而且,维持表皮通透屏障功能在最佳水平有利于预防某些皮肤病的发生;改善皮肤屏障功能有助于某些皮肤病的治疗。     

主观皮肤类型与皮肤屏障功能的关系

目的:比较不同主观皮肤类型(油性、中性和干性皮肤)屏障功能指标的差异。方法:利用无创性方法对自评为油性、中性和干性皮肤的20~25岁北京城市女性(各30例)进行皮脂分泌率(SER)、角质层含水量、p H值和经皮肤水分丢失(TEWL)值的检测,并采用胶带连续粘脱后监测TEWL值变化的方法评价角质层完整性,采用角质层取样蛋白定量的方法评价角质层黏合力和丝氨酸蛋白酶活性。结果:主观皮肤类型为中性皮肤者具有最佳的屏障功能;干性皮肤和油性皮肤者面颊部的屏障功能均有不同程度的受损,表现为TEWL值明显升高、p H值升高、丝氨酸蛋白酶活性增加;但二者也有区别,油性皮肤者角质层完整性下降更明显,而干性皮肤主要是角质层黏合力明显减弱。结论:自评为油性和干性皮肤者与中性皮肤者相比,屏障功能均存在一定程度的缺陷,油性皮肤与干性皮肤均具有不同特点,且与其屏障受损的机制不同有关。     

Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin

Orange peel extract appears to exhibit beneficial effects on skin whitening, inflammation, UVB protection, as well as keratinocyte proliferation. In the present study, we determine whether topical hesperidin influences epidermal permeability barrier function and its underlying mechanisms. Hairless mice were treated topically with 2% hesperidin or 70% ethanol alone twice daily for 6 days. At the end of treatment, basal transepidermal water loss (TEWL) was measured 2 and 4 h post barrier disruption. Epidermal proliferation and differentiation were evaluated by immunohistochemical staining and Western blot analysis. Additionally, lamellar body density and secretion were assessed by electron microscopy. Although there were no significant differences in basal barrier function, in comparison with control animals, topical hesperidin significantly accelerated barrier recovery at both 2 and 4 h after acute barrier abrogation. Enhanced barrier function in hesperidin-treated skin correlated with stimulation of both epidermal proliferation and differentiation, as well as enhanced lamellar body secretion. These results indicate that topical hesperidin enhances epidermal permeability barrier homeostasis at least in part due to stimulation of epidermal proliferation, differentiation, as well as lamellar body secretion.     

Influence of surfactant mixtures on intercellular lipid fluidity and skin barrier function

Background/aims: Surfactant mixtures are used in cosmetic and pharmaceutical formulas in order to establish product efficacy while maintaining mildness and skin lipids. The electron paramagnetic resonance (EPR) technique of the spin labeling method with a nitroxide spin probe is a valuable method in the study of biological membranes. The objective of this study was to define the influence of surfactant mixtures on intercellular lipid fluidity and correlate EPR spectral data with in vivo safety data. Methods: EPR experiment: EPR spectra of 5-doxyl stearic acid (5-DSA) labeled stratum corneum treated with sodium lauryl sulfate (SLS), sodium lauroyl glutamate (SLG) and their mixtures were measured and order parameters were calculated. Clinical testing: Fifteen healthy volunteers free of skin disease and with no history of atopic dermatitis were treated with SLS solutions (0.25%, 0.50%, 0.75%, 1.00%), 1.00% SLG solution and 1.00% surfactant mixture solutions: 0.75% SLS+0.25% SLG, 0.50% SLS+0.50% SLG, 0.25% SLS+0.75% SLG. One hundred μl of solution was applied using a polypropylene chamber for 24 h. Transepidermal water loss (TEWL) was measured with an evaporimeter before and after the application of surfactant solutions and each site was also visually graded according to Lee (1). Results: The order parameter (S) calculated from 1.00 %wt SLS treated stratum corneum was 0.56 ± 0.03, indicating disordering of lipid structure. On the contrary, the high S value (0.82 ± 0.02) for 1.00 %wt SLG suggests a reduced effect on the structured lipid, almost equaling the value of water. Treatment with 0.25 %wt, 0.50 %wt and 0.75 %wt SLS solutions revealed intermediate levels between 1.00 %wt SLG and SLS. The order parameters at each SLS concentration (0.25, 0.50, 0.75 and 1.00 %wt SLS) with 1.00 %wt SLG showed higher values than those of SLS only solutions. There were statistically significant differences between with and without 1.00 %wt SLG (P < 0.05). These results suggest that the addition of 1.00 %wt SLG inhibits the fluidization of intercellular lipid induced by SLS. The visual scores and TEWL values of 1.00% SLG solution were lower than those of the other test solutions (except for the vehicle control: deionized water). The 1.00% surfactant mixture solutions showed lower visual scores and TEWL values of the 1.00% SLS solution. An increase of SLG concentration decreased the visual scores and TEWL values. Order parameter S obtained from EPR spectra correlated with the clinical study. The correlation coefficient (r²) of visual score and TEWL values was 0.73 and 0.83, respectively. Conclusion: SLS disorder (fluidity) intercellular lipids at low concentrations, such as 0.25 %wt, presumably due to the SLS molecules being intercalated into the intercellular lipids. However, EPR spectral data suggest that the addition of 1.00 %wt SLG to an SLS solution (<1.00 %wt) inhibits the fluidization of intercellular lipid induced by SLS. A reasonable correlation between order parameters and human clinical data (visual scores and TEWL values) was observed (r²=0.73 and 0.83, respectively). The use of the EPR spin labeling method for predicting the fluidity of stratum corneum should give further insight into the mechanism of epidermal barrier disruption by surfactants and possibly other chemicals.     

Effect of moisturizers on epidermal barrier function

A daily moisturizing routine is a vital part of the management of patients with atopic dermatitis and other dry skin conditions. The composition of the moisturizer determines whether the treatment strengthens or deteriorates the skin barrier function, which may have consequences for the outcome of the dermatitis. One might expect that a patient's impaired skin barrier function should improve in association with a reduction in the clinical signs of dryness. Despite visible relief of the dryness symptoms, however, the abnormal transepidermal water loss has been reported to remain high, or even to increase under certain regimens, whereas other moisturizers improve skin barrier function. Differing outcomes have also been reported in healthy skin: some moisturizers produce deterioration in skin barrier function and others improve the skin. Possible targets for barrier-influencing moisturizing creams include the intercellular lipid bilayers, where the fraction of lipids forming a fluid phase might be changed due to compositional or organizational changes. Other targets are the projected size of the corneocytes or the thickness of the stratum corneum. Moisturizers with barrier-improving properties may delay relapse of dermatitis in patients with atopic dermatitis. In a worst-case scenario, treatment with moisturizing creams could increase the risks of dermatitis and asthma.     

A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin

The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to deliver nicotinic acid to skin without vasodilatation, on subjects with photodamaged skin have been studied. MN increased skin cell nicotinamide adenine dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of nicotinic acid to skin. Relative to placebo, MN treatment of photodamaged facial skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and increased epidermal thickness by approximately 20% (P = 0.001). In two separate studies, MN treatment increased rates of epidermal renewal by 6% (P = 0.003) to 11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and 10% (P = 0.05) relative to placebo. MN treatment resulted in reductions in the rates of transepidermal water loss (TEWL) of approximately 20% relative to placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects. Results of a tape stripping challenge before and after MN treatment demonstrated a significant correlation (P = 0.03) between increased skin NAD content and resistance to changes in TEWL for MN treated but not placebo subjects. Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects. The results indicate that MN enhances epidermal differentiation and barrier function in skin, suggesting that this method of nicotinic acid delivery may prove useful in limiting progression of actinic skin damage and possibly in treating other conditions involving skin barrier impairment.     

Psychological stress and epidermal barrier function

The skin is the organ that acts as a barrier between the outer and inner environments of the body. It is thus exposed not only to a wide variety of physical, chemical, and thermal insults from the outside world but also to inner endogenous stimuli. Stress, once an abstract psychologic phenomenon, has taken research's center stage in recent years. The "mind-body connection" is now less of an obscure New Age term and more of an elaborate physiologic pathway by which bilateral communication occurs between body and brain. Dermatologists and dermatologic patients have long acknowledged the effect of stress on the skin and its capability to initiate, maintain, or exacerbate several skin diseases. Because disruption of epidermal barrier integrity may be important in the development of some common skin diseases, it is crucial to understand its vulnerability to psychologic stress.     

Moisturization and skin barrier function

ABSTRACT:  Over the past decade, great progress has been made toward elucidating the structure and function of the stratum corneum (SC), the outermost layer of the epidermis. SC cells (corneocytes) protect against desiccation and environmental challenge by regulating water flux and retention. Maintenance of an optimal level of hydration by the SC is largely dependent on several factors. First, intercellular lamellar lipids, organized predominantly in an orthorhombic gel phase, provide an effective barrier to the passage of water through the tissue. Secondly, the diffusion path length also retards water loss, since water must traverse the tortuous path created by the SC layers and corneocyte envelopes. Thirdly, and equally important, is natural moisturizing factor (NMF), a complex mixture of low-molecular-weight, water-soluble compounds first formed within the corneocytes by degradation of the histidine-rich protein known as filaggrin. Each maturation step leading to the formation of an effective moisture barrier—including corneocyte strengthening, lipid processing, and NMF generation—is influenced by the level of SC hydration. These processes, as well as the final step of corneodesmolysis that mediates exfoliation, are often disturbed upon environmental challenge, resulting in dry, flaky skin conditions. The present paper reviews our current understanding of the biology of the SC, particularly its homeostatic mechanisms of hydration.     

Effect of soaps and detergents on epidermal barrier function

The past decade has witnessed an explosion of new impartial information about the complex interaction of the skin with topically applied substances, including soaps and detergents. Despite of all these new data, our knowledge on the exact pathomechanism and molecular events leading to detergent-induced barrier dysfunction remains incomplete and the answers continue to elude us. The longtime prevailing opinion which contends that the damaging effect of soaps and detergents is related to their property to extract and remove useful intercellular lipids has mostly been abandoned. Although this effect might be involved in the damaging effect, it is definitely not the sole mechanism, nor, indeed, is it even the main one. Skin proteins damage, the interaction with keratins and their denaturation, swelling of cell membranes and collagen fibers, cytotoxicity expressed with cellular lysis are other important mechanisms. One proposed mechanism is that an initial stratum corneum hyper-hydration results from a continuous disruption of the secondary and tertiary structures of keratin protein by surfactants, exposing new water-binding sites, thereby increasing the hydration of the membrane. Following evaporation of excess water, the denatured keratin possesses a decreased water-binding capacity and decreased ability to function as a barrier. Recent studies have also emphasized the effects of detergents on lipid synthesis, on lipid-metabolizing enzymes and on keratinocyte differentiation.     

Skin barrier function, epidermal proliferation and differentiation in eczema

Skin permeability barrier function is impaired in eczema, particularly in contact and atopic dermatitis (AD). In contact dermatitis disruption of the barrier by irritants and allergens is the primary event, followed by sensitization, inflammation, increased epidermal proliferation and changes in differentiation. Genetically impaired skin barrier function is already present in non-lesional and more pronounced in lesional skin in AD. Increased epidermal proliferation and disturbed differentiation, including changes in lipid composition, cause impaired barrier function in AD. Defective permeability barrier function enables the enhanced penetration of environmental allergens into the skin and initiates immunological reactions and inflammation. Barrier dysfunction is therefore crucially involved in the pathogenesis of AD. The atopic syndrome represents a genetically impaired skin barrier function as well as impaired nasal, bronchial, and intestinal mucous membranes leading to AD, allergic rhinitis, bronchial asthma or aggravation of AD. Common treatment strategies for eczema include the application of lipid-based creams and ointments, which aim toward the restoration of the defective permeability barrier, thus helping to normalize proliferation and differentiation.     

Effects of skin surface temperature on epidermal permeability barrier homeostasis

Members of the transient receptor potential (TRP) family are temperature sensors, and TRPV1, V3, and V4 are expressed in epidermal keratinocytes. To evaluate the influence of these receptors on epidermal permeability barrier homeostasis, we kept both hairless mouse skin and human skin at various temperatures immediately after tape stripping. At temperatures from 36 to 40 degrees C, barrier recovery was accelerated in both cases compared with the area at 34 degrees C. At 34 or 42 degrees C, barrier recovery was delayed compared with the un-occluded area. 4Alpha-phorbol 12,13-didecanone, an activator of TRPV4, accelerated barrier recovery, whereas ruthenium red, a blocker of TRPV4, delayed barrier recovery. Capsaicin, an activator of TRPV1, delayed barrier recovery, whereas capsazepin, an antagonist of TRPV1, blocked this delay. 2-Aminoethoxydiphenyl borate and camphor, TRPV3 activators, did not affect the barrier recovery rate. As TRPV4 is activated at about 35 degrees C and above, whereas TRPV1 is activated at about 42 degrees C and above, these results suggest that both TRPV1 and TRPV4 play important roles in skin permeability barrier homeostasis. Previous reports suggest the existence of a water flux sensor in the epidermis, and as TRPV4 is known to be activated by osmotic pressure, our results indicate that it might be this sensor.     

Neonatal skin barrier: structure, function, and disorders

The development of the human skin from intrauterine to extrauterine life is a balletic interplay of maturing layers and interlocking structures. We discuss this transition and then branch out to touch on issues of premature infant as well as neonatal skin care. Disruption of the barrier function due to toxins and development errors are expounded upon. Staph scalded skin syndrome, collodion membrane, bullous congenital ichthyosiform erythroderma, autosomal recessive ichthyosis (lamellar and congenital ichthyosiform erythroderma), and harlequin fetus are used as examples of these disruptions. Discussion of therapy with the authors' experience highlights each disease.     

A topical Chinese herbal mixture improves epidermal permeability barrier function in normal murine skin

Chinese herbal medicine (CHM) has been shown to have beneficial effects for both skin disorders with barrier abnormality and as skin care ingredients. Yet, how CHM exerts their benefits is unclear. As most, if not all, inflammatory dermatoses are accompanied by abnormal permeability barrier function, we assessed the effects of topical CHM extracts on epidermal permeability barrier function and their potential mechanisms. Topical CHM accelerated barrier recovery following acute barrier disruption. Epidermal lipid content and mRNA expression of fatty acid and ceramide synthetic enzymes increased following topical CHM treatment in addition to mRNA levels for the epidermal glucosylceramide transport protein, ATP-binding cassette A12. Likewise, CHM extract increased mRNA expression of antimicrobial peptides both in vivo and in vitro. These results demonstrate that the topical CHM extract enhances epidermal permeability barrier function, suggesting that topical CHM could provide an alternative regimen for the prevention/treatment of inflammatory dermatoses accompanied by barrier abnormalities.     

紫外线照射对表皮屏障功能的影响

 表皮屏障在抵御外界危险因素侵害的过程中发挥重要作用。表皮屏障中各组成部分的结构及功能失调与人类的多种皮肤疾病有关。紫外线辐射等因素可引起表皮屏障功能障碍,紫外线照射使表皮屏障变得更易渗透,经皮水丢失量增加,病原体和过敏原更易进入体内,其机制可能与角质层屏障中角化包膜结构蛋白、细胞外脂质与天然保湿因子的含量降低,以及颗粒层中紧密连接屏障功能的减弱有关。近年来一些研究拓展了紫外线照射对表皮屏障的结构与功能影响的认识,本文综述紫外线照射与表皮屏障功能的影响。     

Influence of skin area,age and sex on corneometric determinations

Background/aims: Comeometry represents a useful tool for dermatologists, even though several interfering variables may reduce its reliability level. The present study describes some of the methodological points that optimize corneometric measurements and analyzes the interference due to the skin area selected, the age and the sex of the individuals observed. Results: The results show that skin areas may present significantly different corneometric values. In addition, a significant correlation of the corneometric values at most of the sites was observed independently of the sun-exposed site. Conclusions: The corneometric values were clearly age dependent and sex independent. Measurements were obtained from eight different body areas (two of them were symmetric and presented superimposable results). The volar forearm appears to be the area least influenced by the patients’age and presents the lowest correlation coefficients with other skin sites.     

In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site

BACKGROUND: The knowledge of epidermal thickness (ET) is of great significance in many areas of medical and biological research. OBJECTIVES: We aimed to assess optical coherence tomography (OCT) in terms of precision, and to investigate the influence of several constitutional factors, such as age, gender, skin type, and anatomic site, on the mean ET using OCT in vivo. METHODS: Eighty-three subjects were studied using OCT in vivo. Intra- and inter-day repeatability measurements were performed. The mean ET was assessed in six different body sites of young (20-40 years old) and old (60-80 years old) Caucasians, respectively. An ethnic group was included into the study. RESULTS: OCT proved to be a precise technique in terms of repeatability and reproducibility as expressed in low coefficients of variation. Comparison of young and old Caucasians demonstrated a significant decrease of ET with age in all anatomic sites investigated. ET assessed in males and females did not significantly differ, except for forehead skin which is significantly thinner in old females than in males. ET observed in Caucasians did not significantly differ from ET measured in ethnic individuals. Anatomic sites insignificantly influenced ET on an inter-individual level. However, differences of ET between body sites on an intra-individual level are significant. CONCLUSIONS: This was the first systematic in vivo study on ET investigating several influencing parameters of the epidermal dimension in a reasonable study sample by means of OCT. The results presented here may serve as ET reference data in a variety of clinical and experimental matters.     

The impact of obesity on skin disease and epidermal permeability barrier status

Background Obese subjects frequently show skin diseases. However, less attention has been paid to the impact of obesity on skin disorders until now. Objective The purposes of this study are: to highlight the incidence of some dermatoses in obese subjects and to study the water barrier function of the obese skin using transepidermal water loss (TEWL). Methods Sixty obese subjects and 20 normal weight volunteers were recruited. Obese group was further divided into three body mass index (BMI) classes: class I (BMI 30–34.9 kg/m²), class II (BMI 35–39.9 kg/m²) and class III (BMI 40 g/m²). All subjects attended dermatological examination for skin diseases. To assess barrier function, TEWL measurements were performed on the volar surface of the forearm using a tewameter. Results The results of this study showed that: (i) obese subjects show a higher incidence of some dermatoses compared with normal‐weight controls; in addition the dermatoses are more, frequent as BMI increases; (ii) the rate of TEWL is lower in obese subjects, than in the normal‐weight subjects, particularly in patients with intra‐abdominal obesity. Conclusion Specific dermatoses as skin tags, striae distensae and plantar hyperkeratosis, could be considered as a cutaneous stigma of severe obesity. The low permeability of the skin to evaporative water loss is observed in obese subjects compared with normal weight control. Although the physiological mechanisms are still unknown, this finding has not been previously described and we believe that this may constitute a new field in the research on obesity.     

表皮通透屏障功能与表皮CD44表达关系的研究

目的:研究表皮通透屏障功能破坏后表皮CD44的表达.方法:外用胶带破坏裸鼠躯干部表皮通透屏障功能,分别于30min、1 h、3 h、6 h、24 h和48 h后取皮肤标本,用免疫组化的方法观察CD44在表皮的表达.结果:在表皮通透屏障功能破坏后30 min,表皮CD44的表达明显上调;1 h和3 h后,恢复至正常水平;6 h后,表皮CD44的表达又明显增强,并持续到48 h;人为地纠正屏障功能(封包)对表皮CD44的表达没有明显影响.结论:表皮通透屏障功能破坏后,表皮CD44的表达增强,其表达的改变与屏障功能本身无显著相关性.     

外用糖皮质激素对皮肤屏障系统的影响

短期局部外用糖皮质激素会明显降低皮肤屏障功能的恢复速度,长期使用糖皮质激素则会引起屏障结构的改变。外用糖皮质激素对皮肤屏障的破坏机制众多,其中包括抑制角质形成细胞增殖,影响角蛋白、中间丝聚合蛋白的分化、影响角化桥粒、角质形成细胞间质的形成等。因此,在糖皮质激素依赖性皮炎的治疗及使用糖皮质激素进行疾病的治疗中应适当使用皮肤屏障保护产品。