β-防御素2与皮肤病

人β-防御素2是近年来在人体发现的内源性抗菌肽,具有广谱高效的抗菌活性和独特的作用机制.在皮肤疾病的研究中发现,银屑病、寻常痤疮、疣、皮肤癣菌病、基底细胞癌等疾病中,人β-防御素2表达上调.而特应性皮炎患者对细菌和病毒感染的易感性可能与人β-防御素2表达下调或不表达有关.对人β-防御素2的研究将为皮肤疾病的预防和临床治疗提供一个新的方向.     

Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus

Background. There is mounting evidence that antimicrobial peptides have an important role in cutaneous defence, but the expression of these antimicrobial peptides in atopic eczema (AE) is still unclear. There are several families of antimicrobial peptides, including cathelicidins and human β‐defensins. Patients with AE are more susceptible to severe cutaneous viral infections, including varicella zoster virus (VZV). Aim. To characterize the functional activity of the antimicrobial peptides LL‐37 (human cathelicidin) and human β‐defensin (hBD)‐2 keratinocytes were infected with VZV, in a skin‐infection model. Methods. Flow‐cytometry analysis was used to investigate LL‐37 expression in normal human keratinocytes, and quantitative PCR was used to determine viral loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL‐37 and hBD‐2. Results. LL‐37 expression was present in keratinocytes, and both exogenous LL‐37 and hBD‐2 significantly reduced VZV load in infected keratinocytes and B cells. Specific antibodies blocked the antiviral action exhibited by these antimicrobial peptides. Pre‐incubation of VZV with LL‐37, but not hBD‐2, further reduced VZV load. Conclusions. Both LL‐37 and hBD‐2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE.     

Mechanical and metabolic injury to the skin barrier leads to increased expression of murine β-defensin-1, -3, and -14

Protection of the skin against microbiological infection is provided by the permeability barrier and by antimicrobial proteins. We asked whether the expression of murine β-defensins (mBDs)-1, -3, and -14-orthologs of human β-defensins hBD-1, -2, and -3, respectively--is stimulated by mechanically/physicochemically (tape stripping or acetone treatment) or metabolically (essential fatty acid-deficient (EFAD) diet) induced skin barrier dysfunction. Both methods led to a moderate induction of mBD-1 and mBD-14 and a pronounced induction of mBD-3 mRNA. Protein expression of the mBDs was increased as shown by immunohistology and by western blotting. Artificial barrier repair by occlusion significantly reduced the increased expression of mBD-14 after mechanical injury and of all three mBDs in EFAD mice, supporting an interrelationship between permeability and the antimicrobial barrier. mBD-3 expression was stimulated in vitro by tumor necrosis factor-α (TNF-α), and a neutralizing anti-TNF-α antibody significantly reduced increased mBD-3 expression after barrier injury in mouse skin, indicating that induction of mBD-3 expression is mediated by cytokines. The expression of mBD-14 was stimulated by transforming growth factor-α and not by TNF-α. In summary, we demonstrated upregulation of mBD1, -3, and -14 after mechanically and metabolically induced skin barrier disruption, which may be an attempt to increase defense in the case of permeability barrier dysfunction.     

丹参酮对寻常性痤疮皮损组织β防御素-2 mRNA表达的影响

目的探讨寻常性痤疮皮损中人β防御素-2(HBD-2)mRNA的表达情况及丹参酮对其的影响。方法选择40例寻常性痤疮患者于口服丹参酮治疗前、后分别评价疗效及不良反应,同时取背部皮损,用逆转录聚合酶链反应法(RT-PCR)检测HBD-2 mRNA的表达情况,并与20名健康人进行比较。结果治疗组治疗前、后皮损及正常对照组均可检测到HBD-2 mRNA的表达,患者皮损部位表达明显高于非皮损部位和对照组,差异有显著性意义(P<0.01),治疗后患者皮损中HBD-2 mRNA表达比治疗前显著下降(P<0.01),但明显高于非皮损部位和正常对照组(P<0.01)。治疗后患者非皮损部位HBD-2 mRNA表达较治疗前升高(P<0.05)。结论丹参酮有抗炎、杀菌的功能,还可保持患者皮损局部HBD-2 mRNA的较高浓度表达,增强对寻常性痤疮患者的抗炎作用。     

β2AR antagonists and β2AR gene deletion both promote skin wound repair processes

Skin wound healing is a complex process requiring the coordinated, temporal orchestration of numerous cell types and biological processes to regenerate damaged tissue. Previous work has demonstrated that a functional β-adrenergic receptor autocrine/paracrine network exists in skin, but the role of β2-adrenergic receptor (β2AR) in wound healing is unknown. A range of in vitro (single-cell migration, immunoblotting, ELISA, enzyme immunoassay), ex vivo (rat aortic ring assay), and in vivo (chick chorioallantoic membrane assay, zebrafish, murine wild-type, and β2AR knockout excisional skin wound models) models were used to demonstrate that blockade or loss of β2AR gene deletion promoted wound repair, a finding that is, to our knowledge, previously unreported. Compared with vehicle-only controls, β2AR antagonism increased angiogenesis, dermal fibroblast function, and re-epithelialization, but had no effect on wound inflammation in vivo. Skin wounds in β2AR knockout mice contracted and re-epithelialized faster in the first few days of wound repair in vivo. β2AR antagonism enhanced cell motility through distinct intracellular signalling mechanisms and increased vascular endothelial growth factor secretion from keratinocytes. β2AR antagonism promoted wound repair processes in the early stages of wound repair, revealing a possible new avenue for therapeutic intervention.     

表皮抗菌肽的研究进展

抗菌肽是在多种生物体中表达的具有抗菌活性的肽类物质总称.皮肤频繁与环境中的微生物接触而不被感染,表皮抗菌肽起了重要作用.人类表皮抗菌肽主要包括防御素和cathelicidin家族的LL-37,由于其具有普通抗生素所不具有的一系列优点,使其生物学活性和与皮肤屏障的关系成为目前研究的热点,对其深入研究为抵御疾病、延缓衰老、相关皮肤病的发病机制及治疗等方面带来了新的希望.     

白念珠菌对角质形成细胞β防御素-2 mRNA表达的影响

目的 探讨白念珠菌及其菌体成分对人角质形成细胞β防御素-2表达的影响。方法 采用酶解、反复冻融、超声破碎和超速离心等方法制备真菌成分;用逆转录聚合酶链反应(RT-PCR)方法检测白念珠菌及其菌体成分刺激人角质形成细胞24h后β防御素-2mRNA表达。结果 正常培养的人角质形成细胞和角质形成细胞永生细胞系HaCaT均有β防御素-2mRNA的少量表达,白念珠菌、白念珠菌细胞壁提取物和纯甘露聚糖可以使β防御素-2mRNA表达增强(P值分别<0.01、0.05和0.01),而白念珠菌培养上清液和细胞浆提取物对β防御素-2表达无明显影响(P>0.05)。结论 白念珠菌可上调角质形成细胞β防御素-2mRNA的表达,甘露聚糖可能是起诱导作用的活性成分。角质形成细胞通过表达β防御素-2在皮肤黏膜的抗感染防御机制中发挥重要作用。     

β-防御素在银屑病发病机制中的作用

β-防御素是一组小分子抗菌肽,能够抗多种病原微生物感染,促进炎症反应,并对T细胞等发挥趋化作用.研究发现,银屑病发病可能与β-防御素有关.β-防御素可活化银屑病免疫相关的炎症因子,趋化未成熟的树突细胞和记忆T细胞,并通过促分裂素原活化蛋白激酶作用于角质形成细胞产生炎症因子,将固有性免疫和获得性免疫连接起来.未来应深入探讨β-防御素在银屑病发病中的作用,进一步完善银屑病的免疫学发病机制,寻求治疗新靶点.     

寻常性银屑病患者皮损中抗菌肽LL-37和人β防御素-2 mRNA的表达

目的探讨寻常性银屑病患者皮损中抗菌肽LL-37与人β防御素-2(hBD-2)mRNA的表达.方法应用逆转录(RT)-PCR方法检测31例寻常性银屑病患者皮损和16例正常人皮肤组织中LL-37和hBD-2 mRNA的表达.结果与正常人皮肤组织相比,寻常性银屑病患者皮损中LL-37和hBD-2 mRNA的表达水平明显升高(P＜0.001).结论寻常性银屑病患者皮损中LL-37和hBD-2 mRNA表达水平的上调可能与银屑病患者很少发生皮肤感染等有关.     

Ⅱ型单纯疱疹病毒对HaCaT细胞分泌β防御素mRNA的影响

β防御素是近年来发现的一类小分子内源性抗菌肽,具有广谱抗菌、抗病毒活性,是天然免疫的重要递质,并与获得性免疫有较密切关系.本研究旨在探讨生殖器疱疹病毒感染初期,作为第一道防御屏障的角质形成细胞(KC)分泌β防御素,在防止单纯疱疹病毒(HSV)-Ⅱ感染中的作用.     

存活素和皮肤病

存活素是凋亡抑制蛋白家族的新成员,不仅具有抑制细胞凋亡的能力,而且参与细胞有丝分裂和胞质分离的调节。存活素仅表达于各种皮肤良恶性病变,而不表达于正常皮肤。综述存活素分子结构、抑制凋亡的机制、在细胞分裂中的作用、与各种良恶性增生性皮肤病的关系以及靶向治疗。     

皮肤病住院患者31例死亡回顾性分析

我院皮肤科每年的门诊约有10余万人次,病种繁多,收住院的多是病情较重或复杂的患者,为了解死亡情况,总结经验和教训,对我院皮肤科近18年来31例住院死亡患者的临床资料进行分析.     

2005年度国家自然科学基金皮肤性病学领域评审资助情况分析

概述了2005年度国家自然科学基金(简称自然科学基金)皮肤性病学领域的受理、评审和资助情况,通过对该领域面上项目申请和受资助项目的分析,反映皮肤性病学领域近年来基础研究的发展方向、趋势和存在的问题,并提出建议.供从事皮肤性病学工作的科研人员在申报自然科学基金项目时参考.     

核因子E2相关因子2激活剂及其在皮肤科的应用

核转录相关因子激活剂以核转录相关因子为靶点发挥其抗氧化作用,成为目前最重要的抗氧化剂之一。核转录相关因子激活剂直接或间接激活Nrf2／Keapl系统,诱导抗氧化基因及Ⅱ相解毒酶的表达,提高细胞抗氧化能力,在细胞的防御保护中发挥重要作用。目前体内外研究证实,核转录相关因子激活剂,如（-）-表没食子儿茶素-3-没食子酸酯、姜黄素、莱菔硫烷和阿司匹林等,在日光损伤、白癜风、大疱性皮肤病、伤口愈合、皮肤肿瘤、黄褐斑与银屑病等疾病中起到了较好的治疗作用。     

Nrf2信号通路及其在皮肤病中的应用进展

Nrf2信号通路是缓解细胞氧化应激损伤时最重要的抗氧化应激通路,其转录激活过程是整个氧化应激过程关键步骤,在抵抗外界氧化应激损伤过程中维持体内氧化还原平衡,提高细胞抗氧化应激能力中发挥重要作用。本文将概述Nrf2信号通路在皮肤病中的应用和研究进展。     

皮肤肿瘤中Wnt/β-连环蛋白信号通路的研究进展

Wnt/β-连环蛋白信号通路的异常活化常与皮肤肿瘤的发生发展密切相关.导致通路异常的因素较多,如分泌性Wnt蛋白失调;通路蛋白分子或旁路调控分子的突变;病毒感染和其他通路交叉影响等.通路的致瘤机制及对肿瘤的生物学影响还存在组织特异性,而皮肤肿瘤种类多,且组织来源广泛.因此探索Wnt通路在皮肤肿瘤中差异及组织特异性将对肿瘤靶向治疗研究有指导意义.

Abstract：

The abnormal activation of Wnt/β-catenin signaling pathway is usually and closely related to the occurrence and development of cutaneous tumors.There are various factors causing the abnormality of this pathway, such as deregulated expression of secreted Wnt protein, mutations of proteins involved in this pathway or regulatory molecules in bypass pathway, viral infection, interaction with other pathways, and so on.In addition, the tumorigenic mechanisms of this pathway and its biologcal effects on tumors are considered to be tissue-specific.However, the types and tissue origins of cutaneous tumors are various.Therefore, exploring the disparities and tissue specificity of Wnt pathway in cutaneous tumors will provide a guide to the targeted therapy of tumors.     

中国12城市0～7岁儿童皮肤病患病率调查

目的 调查中国城市0～7岁学龄前儿童皮肤病患病率.方法 2014年11月至2015年4月选择我国12个城市作为调查点,以0～7岁学龄前儿童为调查对象,采用以人群为基础的随机分层抽样,并以40个预防接种门诊和84个幼儿园为调查现场.由经过培训的皮肤科医师完成问卷调查和皮肤科体检.结果 共调查20033人,年龄0.08～6.83(2.41±1.82)岁.7 823人患有皮肤病,总患病率为39.05％,12城市患病率依次为大连66.96％、上海56.73％、武汉55.49％、太原49.18％、成都47.16％、南京41.93％、重庆41.03％、合肥35.98％、深圳33.87％、长沙31.37％、北京23.52％、沈阳(13.42％).共调查40种皮肤病,在调查的20 033人中,患病率最高的10种疾病依次是湿疹/婴儿湿疹/特应性皮炎(18.71％,3 749例)、寻常型鱼鳞病(6.25％,1 253例)、毛发苔藓(5.73％,1 148例)、尿布皮炎(5.29％,1 059例)、丘疹性荨麻疹(5.25％,1 052例)、血管瘤/血管畸形(3.86％,774例)、白色糠疹(3.45％,691例)、感染性皮肤病(2.59％,519例)、荨麻疹(1.72％,344例)和接触性皮炎(0.5％,100例).结论 中国城市学龄前儿童人群中皮肤病总患病率达39.05％,以湿疹/特应性皮炎最为常见.     

环氧合酶2在人恶性黑素瘤中高表达

目的 探讨恶性黑素瘤组织及黑素瘤细胞系中环氧合酶2(COX-2)的表达及意义.方法 免疫组化法比较性研究25例皮内痣、45例恶性黑素瘤COX-2蛋白的表达情况.并结合患者的临床资料进行分析.同时,免疫印迹法检测正常黑素细胞及3种黑素瘤细胞系中COX-2蛋白的表达情况.结果 在恶性黑素瘤中,COX-2蛋白阳性表达率为80%(36/45),显著高于皮内痣组0%(0/25)(P<0.05);肿瘤组织中COX-2蛋白表达与淋巴结转移、TNM分期密切相关(P<0.05).正常黑素细胞COX-2阴性表达,3种恶性黑素瘤细胞系中A375、1585细胞COX-2表达水平明显升高,而Libr细胞未见阳性表达.结论 COX-2在恶性黑素瘤组织及细胞系中表达率显著升高,可能在恶性黑素瘤发生发展中具有一定作用.     

新型冠状病毒肺炎疫情期间医护人员皮肤损伤流行病学调查及特征分析

【摘要】 目的 调查抗击新型冠状病毒肺炎（COVID-19）疫情的一线医护人员皮肤损伤流行病学特征。方法 设计调查问卷,并通过“问卷网”网站发布问卷,于2020年3月10 - 20日通过微信向解放军中部战区总医院收治COVID-19确诊患者的6个感染病区病房的一线医护人员推送问卷。回收问卷,建立数据库,对医护人员的皮肤损伤发生率、损伤类型及流行病学特征进行统计分析。结果 共调查约550名医护人员,收集调查问卷404份,有效问卷391份,其中303例出现皮肤损伤。调查结果显示,女性、手部清洁频率＞10次/d、穿戴三级防护装备时长＞6 h/周均是出现皮肤损伤的危险因素,经常使用护手霜可减少皮肤问题的发生。被调查者中女性皮肤损伤发生率为79.81%（249/312）,男性为38.35%（54/79）（χ2 = 4.741,P = 0.029）。手部清洁频率10 ~ 20次/d组［79.73%（118/148）］及＞20次/d组（85.71%,84/98）皮肤损伤发生率高于1 ~ 10次/d组［69.66%（101/145）,χ2 = 9.330,P = 0.009］。穿戴防护装备时长1 ~ 5 h/周组皮肤损伤发生率（64.04%,73/114）低于6 ~ 10 h/周组（81.48%,66/81）、11 ~ 15 h/周组（95.24%,20/21）、16 ~ 20 h/周组（81.82%,36/44）、21 ~ 25 h/周组（86.49%,32/37）、＞25 h/周组（80.85%,76/94）,差异有统计学意义（χ2 = 19.164,P = 0.002）。391例被调查者中,消毒和防护装备相关皮肤损害集中表现为皮肤干燥（72.89%）、脱屑（56.78%）、皮肤压力性损伤（54.48%）、皮肤浸渍（45.01%）、敏感性皮肤（33.50%）,相关皮肤病按照发生率由高到低依次为痤疮（27.11%）、面部皮炎（23.27%）、湿疹皮炎（21.48%）、毛囊炎（18.92%）、皮肤真菌病（11.00%）、荨麻疹（9.21%）等。结论 抗击COVID-19的一线医护人员防护装备相关皮肤损伤发生率高,加强皮肤的保护措施可以显著降低皮肤损伤的发生率。