皮肤屏障与银屑病研究进展

皮肤作为人体的第一道防线,对抵御外界有害因素的损伤以及维持人体内环境的稳态有着至关重要的作用。皮肤屏障的结构和功能与一些皮肤病的发生发展有着重要的联系。研究发现皮肤屏障功能受损可能是银屑病发生的重要诱因,然而皮肤屏障缺陷与银屑病发生的确切机制仍不清楚。该文主要对近年来皮肤屏障与银屑病的研究进展作一综述。     

含青刺果油和马齿苋的舒敏保湿特护霜修复敏感性皮肤的屏障功能评估

敏感性皮肤（sensitive skin,SS）常见于一般人群,特指皮肤在受到外界刺激后易出现瘙痒、灼热、刺痛、紧绷等不适感,伴或不伴红斑、脱屑等客观体征,主要发生于面部［1?2］。各地报道的SS流行率不等,女性SS介于50％ ~ 61％之间,男性30％ ~ 44％［3］。痤疮、玫瑰痤疮、激素依赖性皮炎等面部皮肤病也常合并不同程度皮肤敏感［3］。临床医生在对面部皮肤病诊治过程中易忽视皮肤屏障功能修复。为了评估含青刺果油、马齿苋舒敏保湿特护霜对不同类型SS皮肤屏障的修复作用,我们对60例SS进行自身对照临床观察,报道如下……     

含透明质酸及白藜芦醇成分护肤品对干性皮肤屏障功能的影响

目的研究含有透明质酸和白藜芦醇的安特柔产品对于干性皮肤屏障功能的影响及保湿效果。方法入选皮肤中度干燥的女性受试者32例,采用自身左右对照的方法,比较安特柔沐浴洗发露与普通洁肤香皂清洁后皮肤屏障功能的差别,遂后使用安特柔保湿霜,观察6 h后及连续试用产品1周后皮肤屏障功能指标的变化。结果相比普通洁肤香皂清洁,安特柔产品清洁后皮肤经皮水分丢失(TEWL)不但没有升高反而下降(P0.05),pH值升高程度低于普通洁肤香皂(P0.05),角质层含水量轻微增加但差异无统计学意义(P=0.480);安特柔保湿霜单次使用后6 h,身体左右两侧皮肤角质层含水量均明显提高、TEWL下降,与基线相比P0.05,皮肤p H值均恢复到基线水平(P=0.094)。连续使用安特柔沐浴洗发露和保湿霜1周后,角质层含水量较基线进一步增加,较单次使用后6 h也有轻度的增加(P0.05);TEWL继续下降,p H值继续维持在偏酸范围内。连续使用1周后干性皮肤者皮肤的光滑度、干燥度和脱屑等均有显著改善;受试者自我评价50%的人认为皮肤的光滑度、干燥度、瘙痒和鳞屑有中度以上改善。结论安特柔系列产品具有很好的保湿效果和帮助屏障功能恢复的作用,单次使用后6 h仍有效,长期使用能很好地改善皮肤干燥。     

Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate

BACKGROUND: Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin. OBJECTIVES: We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin. METHODS: The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema. RESULTS: The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness. CONCLUSIONS: We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.     

类人胶原蛋白敷料治疗面部脂溢性皮炎疗效观察及对皮肤屏障功能的影响

目的探讨类人胶原蛋白敷料治疗面部脂溢性皮炎的疗效、安全性及其对皮肤屏障功能的影响。方法将20~50岁女性面部脂溢性皮炎患者67例随机入组,试验组患者外用酮康唑乳膏加类人胶原蛋白敷料,对照组患者单独外用酮康唑乳膏,两组患者均用药10 d,观察皮损变化并测定皮肤屏障功能相关指标。结果第2次随访时,试验组症状积分[(1.06±1.06)分]、经皮水分丢失量(transepidermal water loss,TEWL)[(11.99±5.84)g/(m2?h)]均低于对照组[(1.94±1.17)分、(16.17±8.47)g/(m2?h)],角质层含水量(40.20±11.69)高于对照组(34.13±10.86),差异均有统计学意义(P=0.002,0.024,0.033)。两组患者均未出现明显不良反应。结论类人胶原蛋白敷料治疗成年女性面部脂溢性皮炎,能改善皮肤屏障功能,减轻皮损,可以作为面部脂溢性皮炎的一个安全有效的辅助治疗手段。     

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。     

面部痤疮、湿疹、黄褐斑及日光皮炎皮肤屏障功能评价及其临床意义

目的 探讨痤疮、亚急性湿疹、黄褐斑及日光皮炎的皮肤屏障功能的差异.方法 选损容性皮肤病300例,其中痤疮80例,亚急性湿疹80例;黄褐斑80例;日光皮炎60例.健康人60例为对照.运用德国Courage+Khazaha公司的无创性皮肤生理功能测试仪,测量受试者面部皮肤的皮脂含量、角质层含水量和经表皮水分流失值(TWEL).结果 4种损容性皮肤病组与健康对照组相比,痤疮的皮脂含量及TWEL值较健康对照高,角质层含水量较健康对照低,差异有统计学意义(P＜0.01).亚急性性湿疹、日光皮炎及黄褐斑的皮脂含量、角质层含水量均较健康对照组低,TWEL值均较健康对照高,差异有统计学意义(P＜0.01).4种皮肤病组问进行比较,痤疮的皮脂含量比其他3组高,差异有统计学意义(P＜0.01),其余3组间皮脂含量差异无统计学意义(P＞0.05);亚急性湿疹的角质层含水量比痤疮及黄褐斑低,差异有统计学意义(P＜0.01),与日光皮炎的角质层含水量相比,差异无统计学意义(P＞0.05);日光皮炎的角质层含水量比痤疮及黄褐斑低,差异有统计学意义(P＜0.01);痤疮的角质层含水量比黄褐斑低,差异有统计学意义(P＜0.01);黄褐斑的TWEL值比其他3组低,差异有统计学意义(P＜0.01),其余3组TWEL值相比差异无统计学意义(P＞0.05).结论 4种损容性皮肤病皮肤屏障功能均存在损伤,提示恢复皮肤的屏障功能有助于治疗这4种损容性皮肤病.     

青鹏软膏治疗乏脂性湿疹疗效和皮肤屏障功能影响的自身对照研究

目的 探讨青鹏软膏治疗乏脂性湿疹的疗效,以及对皮肤屏障功能的影响。 方法 对78例双下肢对称分布的乏脂性湿疹患者,采取自身对照方法,青鹏软膏组左下肢外用青鹏软膏,丁酸氢化可的松组右下肢外用丁酸氢化可的松乳膏,每日2次,连续治疗4周,比较其疗效及皮肤屏障功能的变化。 结果 治疗1、2周时,青鹏软膏组的有效率低于丁酸氢化可的松组,差异有统计学意义（1周：39.74%比58.97%,χ2 = 5.77,P < 0.05;2周：60.26%比76.92%,χ2 = 5.03,P < 0.05）,但治疗4周时,青鹏软膏组和丁酸氢化可的松组有效率（80.77%比87.18%）差异无统计学意义（P > 0.05）。治疗4周,青鹏软膏组角质层含水量显著高于对丁酸氢化可的松组（P < 0.05）,而治疗2、4周时,青鹏软膏组TEWL值显著低于丁酸氢化可的松组（均P < 0.05）。 结论 青鹏软膏治疗乏脂性湿疹安全、有效,作用稳定,利于皮肤屏障功能的修复。     

Consumption of functional fermented milk containing borage oil, green tea and vitamin E enhances skin barrier function

Abstract:  As emerging studies show that skin functioning can be improved with orally imbibed ingredients, we decided to investigate a mixture of borage oil, catechins, vitamin E and probiotics, all known for their reported effects on epidermal function, in a fermented dairy product, for the first time. Gamma-linolenic acid (GLA) and catechins bioavailability and their effects on skin functionality have not been previously investigated from a fermented dairy product. Firstly, we assessed the bioavailability of GLA and catechins mixed in a fermented dairy matrix by measuring their levels in chylomicrons and plasma samples respectively. For the GLA contained in the dairy matrix, the area under the curve and time for maximal absorption were significantly different to the same kinetic parameters compared with absorption from the free oil indicating improved oral bioavailability. However, the overall absorption of catechins over the 6-h period was identical for both product forms. These results were sufficiently promising to warrant a 24 week skin nutrition intervention study in female volunteers having dry and sensitive skin. The product improved stratum corneum barrier function compared with a control product as early as 6 weeks after the consumption which continued throughout the rest of the study. The reduction in transepidermal water loss relative to control was maintained throughout the trial despite seasonal changes. Moreover, as a result of the enhanced bioavailability, a much greater effect on skin barrier function occurred than reported previously for the individual ingredients. Nevertheless, body mass index significantly influenced various outcome measurements of this study.     

皮肤屏障功能研究进展

皮肤屏障主要由角化包膜和脂质膜、中间丝聚合蛋白、角蛋白、角化桥粒、板层小体和角质层角质形成细胞问质、紧密连接等组成,防止水分的丢失及阻止外界的侵害,维持机体内稳态.基因突变、变应原、微生物、紫外线等因素共同作用下,能导致皮肤屏障结构、代谢及功能的异常,引起鱼鳞病、特应性皮炎等皮肤病.阐明皮肤病与屏障结构及功能异常联系,指导开发有效的诊疗和预防措施.     

微生态和皮肤屏障与头皮屑

头皮屑以头皮脱屑伴瘙痒为特征,病因复杂,主要涉及微生态和皮肤屏障两方面因素。头皮微生态是头皮微生物及其生长环境构成的复杂生态系统,皮肤保护机体免受外界有害因素侵袭和防止组织水分丢失,具有重要的屏障作用。头皮微生物种群及数目的变化会改变皮肤屏障功能,而屏障功能的改变又会对微生物的定植产生影响,二者共同参与头皮屑的发病过程。     

多形性日光疹皮损中板层小体分布、神经酰胺酶表达与皮肤屏障功能

目的 探讨多形性日光疹（PLE）表皮中板层小体的分布、神经酰胺酶的表达与皮肤屏障受损的相关性。方法 选取PLE患者47例及正常人对照40例,通过电镜观察两组皮损处颗粒层、棘层板层小体的数量及分布情况,运用免疫组化测定皮损处神经酰胺酶的表达,采用无创性皮肤测试仪测量皮损处经皮水分丢失（TEWL）、角质层含水量及皮脂含量。结果 透射电镜结果显示：与对照组相比,PLE患者颗粒层、棘层板层小体数量明显少于正常人对照组,分布较正常人对照组紊乱。免疫组化结果显示：PLE患者皮损处神经酰胺酶表达20例阳性、21例弱阳性、6例阴性;正常人对照组中36例阳性、4例弱阳性,差异有统计学意义（P < 0.01）;皮损处TEWL（34.2191 ± 12.70）较正常人对照组（16.8350 ± 6.50）高,角质层含水量（22.7319 ± 8.71）较正常人对照组（29.4250 ± 5.08）低,差异有统计学意义（P < 0.01）;皮脂含量两者之间差异无统计学意义。结论 PLE患者存在神经酰胺合成障碍,可能是皮肤屏障受损的原因之一。     

Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function

We have used microdialysis in the dermis for assessing penetration kinetics of salicylic acid (SA) in healthy volunteers (n = 18), following application on the volar aspect of the left forearm. Penetration was monitored at four locations: in normal (unmodified) skin and in skin with perturbed barrier function from (i) repeated tape stripping (ii) irritant dermatitis from 1 or 2% sodium lauryl sulphate (SLS) for 24 h and (iii) delipidization by acetone. The order of the treatments was randomized according to a latin square design. Epidermal barrier function and skin irritation were assessed in each location using evaporimetry and colorimetry. Transepidermal water loss (TEWL) values confirmed that both mild (acetone), moderate (1% SLS) and severe barrier damage (tape stripping and 2% SLS) had occurred. Microdialysis sampling with two parallel probes in the dermis was performed in each of the four treatment areas for every subject. SA (5% in ethanol) was applied in a chamber glued to the skin overlying the microdialysis probes and sampling was continued for 4 h. SA was detectable in all samples and measurable in all samples from penetration through perturbed skin. Comparing the SA penetration in barrier-perturbed skin with the penetration in unmodified skin in the same subject, the mean SA penetration increase was 2.2-fold in acetone-treated skin (P = 0.012), 46-fold in mild dermatitis and 146- and 157-fold in severe dermatitis and tape stripped skin, respectively (P < 0.001). The penetration of SA significantly correlated with the measurements of barrier perturbation by TEWL (P = 0.01) and erythema (P = 0.02) for each individual. Microdialysis sampling of SA penetration was more sensitive than non-invasive measuring techniques in detecting significant barrier perturbation in acetone-treated skin. A positive dose-response relationship for the percutaneous penetration of SA in response to increasing SLS pretreatment concentrations and thus the degree of irritant dermatitis was found. When analysing data by location on the forearm, a tendency towards an intraregional variation in the reactivity to barrier damage was found, with the most proximal location displaying higher reactivity scores than the most distal location in response to the same barrier perturbation procedures. The penetration of SA was not significantly different between locations. In conclusion, using microdialysis in the dermis to obtain real-time dermal pharmacokinetics in the target organ, this study demonstrates highly increased and differentiated cutaneous penetration of SA in barrier-perturbed skin. The measured drug penetration was demonstrated to correlate with non-invasive quantification of barrier damage.     

Accelerated acquisition of permeability barrier function in the skin of presenilin-1-deficient embryos

Presenilin-1 (PS1) is a transmembrane protein and is responsible for the development of early-onset familial Alzheimer’s disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis and cardiac morphogenesis. We report here that PS1 is involved in the development of skin barrier function. PS1-deficient embryos showed an accelerated acquisition of permeability barrier function at embryonic day 17.5 as manifested by the exclusion of a dye solution. While the expression of β-catenin and epidermal differentiation markers such as keratin 1 and loricrin was not substantially altered, an increased accumulation of E-cadherin was observed immunohistochemically in the mutant skin. These results suggest that PS1 regulates the acquisition of permeability barrier function in the skin.     

特应性皮炎患者皮肤屏障与水闸蛋白1表达的相关性研究

目的 研究特应性皮炎（AD）患者皮肤屏障功能情况,并分析其与水闸蛋白1（claudin-1）表达的相关性。 方法 纳入AD患者和健康人各11例。应用皮肤经表皮失水率测定仪和皮肤高频超声检测仪测定受试者经表皮失水率、表皮厚度与表皮致密度,并用双抗体夹心ELISA法定量检测血清中脱落claudin-1表达量。应用单因素方差分析和t检验比较不同组别之间相关参数的差异;应用Pearson相关系数分析不同参数之间的相关性。 结果 AD患者皮疹部位经表皮失水率为（36.9 ± 34.2） g·m-2·h-1,非皮疹部位为（9.1 ± 6.0） g·m-2·h-1,均高于健康对照［（4.4 ± 3.1） g·m-2·h-1］;AD患者皮疹部位表皮厚度（0.23 ± 0.04） mm,显著高于非皮疹部位［（0.18 ± 0.03） mm］和健康对照［（0.18 ± 0.02） mm］。AD患者皮疹部位有其特征性表皮下低回声带。AD患者claudin-1表达量为（0.80 ± 0.88） ng/ml,显著低于健康人［（1.73 ± 1.85） ng/ml］;claudin-1与表皮厚度显著负相关（r = -0.61）,与经表皮失水率的倒数显著正相关（r = 0.44）。 结论 AD患者损伤的皮肤屏障功能与claudin-1表达相关,屏障功能状态可用经表皮失水率、经表皮失水率倒数和表皮厚度进行定量表述。     

Development of a stratum corneum and barrier function in an organotypic skin culture

The stratum corneum of human skin is responsible for maintaining the epidermal permeability barrier. We have developed a bilayered skin culture (SC) which forms a corneum 35 ± 1 cell layers thick 21 days after being raised to the air-liquid (A/L) interface. By the 7th day after raising to the A/L interface the corneocytes were irregularly shaped and had cross-sectional areas (CSA) of 300 m². By the 21st day the corneocytes had assumed polygonal shapes and had a CSA (100–250 m²) similar to that of human foreskin. The total lipid (TL) content of the corneum averaged 5–7% of the lyophilized weight. Ceramide content increased from 20% of TL at day 7 of A/L interface culture to 30% at day 21. Triglycerides decreased from 43% to 17% of TL during the same period. Free fatty acids comprised 5.5% of TL at day 21 of A/L interface culture. The intercorneocyte spaces contained stacks of lipid lamellae. However, the stacks lacked the Landmann unit repeat. Abnormal lamellar structures were observed in both the intra- and extracorneocyte spaces. Transepidermal water loss (TEWL) was >4 mg/cm² per h throughout the culture period. Lipid supplementation of the culture medium and culturing in a low humidity environment improved barrier function by 50%. However, the effects were not additive. The SC developed a near-normal corneum, but did not achieve barrier competence, due at least partially to abnormalities in lipid composition and organization. Improvement of barrier function with lipid supplementation or low humidity indicates that modifications of the culture environment may facilitate the SC in assembling a permeability barrier equivalent to human skin.     

青鹏软膏对皮肤干燥志愿者及特应性皮炎样小鼠模型皮肤屏障功能的影响

目的 探讨青鹏软膏对皮肤屏障功能的影响及其可能机制.方法 招募12名小腿伸侧皮肤干燥的女性志愿者,青鹏软膏涂于右小腿伸侧(青鹏侧)、青鹏软膏基质涂于左小腿伸侧(基质侧),用药7d.分别于用药前、用药3d及用药7d测定皮肤屏障功能相关指标,如,经表皮失水量(TEWL)及角质层含水量.2,4-二硝基氟苯诱导小鼠背部产生特应性皮炎样改变,分别外用青鹏软膏基质(基质组),50％、75％、100％青鹏软膏治疗(50％、75％、100％青鹏组),每天2次,用药2周后,进行组织病理检查,背部皮褶厚度、TEWL的测定,免疫组化测定表皮丝聚蛋白,外皮蛋白及激肽释放酶7含量.结果 志愿者外用青鹏软膏及其基质,3d、7d后均较治疗前TEWL显著下降(青鹏侧f=2.651、3.615;基质侧t=2.996、3.586,均P＜0.05),含水量显著上升(青鹏侧f=9.029、13.842;基质侧f=5.830、11.299,均P＜ 0.001).青鹏侧及基质侧TEWL、含水量比较,差异无统计学意义(P＞0.05).从外观、皮褶厚度及组织病理看,基质组小鼠与模型组相比,皮炎程度差异不大,各青鹏组小鼠皮炎均有不同程度缓解.基质组、青鹏组TEWL均较模型组下降(P＜0.05),而基质组与青鹏组TEWL比较,差异无统计学意义(P＞0.05).基质组、青鹏组KLK7表达均较模型组下降(P＜0.05),但各治疗组间比较,差异无统计学意义(P＞0.05).结论 青鹏软膏基质有改善皮肤屏障功能的作用.     

特应性皮炎相关细胞因子对皮肤屏障的影响

【摘要】 皮肤是人体最大的器官,是一个重要的屏障。特应性皮炎患者存在皮肤屏障功能异常,同时其细胞因子的组成与健康人不同。在特应性皮炎患者皮肤中发现的许多细胞因子能够影响角质形成细胞的分化和角化过程。本文综述了特应性皮炎相关细胞因子的最新进展及其对皮肤屏障功能的影响,这些结果有利于了解特应性皮炎的发病机制,并可能为特应性皮炎的治疗提供新的方向。     

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。     

中间丝蛋白与特应性皮炎皮肤屏障功能

特应性皮炎的病因复杂,发病机制尚未明确,可能是遗传、环境、皮肤屏障功能缺陷及免疫相互作用的结果.中间丝蛋白基因是表皮分化复合物基因簇的成员之一,与细胞膜形成及表皮终末分化密切相关.中间丝蛋白基因突变是特应性皮炎发病的重要易患因素之一,中间丝蛋白的减少和缺失,可能是引起特应性皮炎等十燥性皮肤病的主要原因.