环状RNA在皮肤相关疾病及创面愈合中的研究进展

环状RNA(circRNA)为一类具有连续共价闭环结构的新型非编码RNA(ncRNA),无3′及5′游离末端。其可作为微小RNA(miRNA)"分子海绵"调节转录或剪接,也可与RNA结合蛋白相互作用,在机体生理和病理过程中都起着关键作用。近来有研究表明,在与创面愈合相关的细胞(血管内皮细胞、角质细胞)增殖、迁移等活动中,有circRNA参与其中。本文回顾了circRNA在不同类型皮肤细胞中发挥的调节作用及其与皮肤相关疾病如皮肤鳞状细胞癌、基底细胞癌、重度痤疮的联系,旨在为阐释创面愈合的细胞分子机制提供新思路,以期为解决临床上创面治疗难题开拓新方向。     

微小核糖核酸对糖尿病足溃疡的作用机制研究及应用进展

糖尿病足溃疡是糖尿病最常见的并发症之一，目前缺乏有效的治疗手段。微小核糖核酸(miRNA)是调节创面愈合的核心因子，通过与靶基因相互作用，参与了糖尿病足溃疡愈合过程中关键细胞(内皮细胞、成纤维细胞、角质形成细胞)的病理反应。本文就这些与糖尿病足溃疡相关的miRNA对关键细胞的作用机制作一综述，并总结了目前通过人工合成特异性miRNA来促进创面愈合的相关实验研究，为临床治疗糖尿病足溃疡提供了新的思路和方法。     

中性粒细胞胞外诱捕网在创面愈合过程中作用的研究进展

创面愈合与免疫及炎症反应密切相关。中性粒细胞作为炎症反应的主要效应细胞之一,已被证明在糖尿病足等创面愈合的病理生理过程中起着重要的作用。尤其是新近研究发现中性粒细胞在炎症、损伤等的刺激下,可以通过释放中性粒细胞胞外诱捕网(NET),抑制或阻碍创面的愈合,在创面愈合过程中起着重要的作用。然而,NET在不同类型的创面愈合中的作用还未完全阐明。本文将围绕免疫反应与炎症反应等在创面愈合中的最新研究进展,就NET在不同类型的创面愈合过程中的作用作一综述。     

三黄生肤油联合硫化氢对糖尿病足模型大鼠的治疗作用

目的:观察三黄生肤油联合硫化氢对糖尿病足(DF)模型鼠的治疗作用。方法:利用链脲佐菌素腹腔注射建立糖尿病大鼠模型,随后利用切除足部皮肤制造DF模型。48只造模成功的DF模型大鼠使用数字表法分为基质对照组、硫化氢组、三黄生肤油组和三黄生肤油+硫化氢组,每组12只。各组大鼠采用相应药剂涂抹创面、2次/天,连续3周。比较四组治疗期间足底皮温、足底痛阈、创面愈合率和创面肉芽组织血管数。结果:治疗后,三黄生肤油+硫化氢组创面愈合率高于基质对照组(1、2、3周,P0.05或P0.01)、硫化氢组和三黄生肤油组(P0.05)。硫化氢组和三黄生肤油组创面愈合率高于基质对照组(2,3周,P0.05),但硫化氢组与三黄生肤油组创面愈合率无显著性差异(P0.05)。治疗前四组足底皮温和足底痛阈无显著性差异(P0.05)。三黄生肤油+硫化氢组治疗2、3周足底皮温高于基质对照组,足底痛阈低于基质对照组(P0.05)。三黄生肤油+硫化氢组治疗3周足底皮温高于硫化氢组和三黄生肤油组,足底痛阈低于硫化氢组和三黄生肤油组(P0.05)。硫化氢组和三黄生肤油组治疗3周足底皮温高于基质对照组,足底痛阈低于基质对照组(P0.05),但硫化氢组和三黄生肤油组间无显著性差异(P0.05)。创面肉芽组织中血管数,三黄生肤油+硫化氢组、硫化氢组和三黄生肤油组均高于基质对照组(P0.05),三黄生肤油+硫化氢组又高于硫化氢组和三黄生肤油组(P0.05)。结论:三黄生肤油联合硫化氢可改善DF模型鼠足底皮温和痛阈,增加创面血管生成,有利于创面的愈合,疗效优于单用三黄生肤油或硫化氢。     

碱性成纤维细胞生长因子与小儿烧伤创面的愈合

背景：皮肤创面愈合是一个复杂的病理过程,对于创伤和创伤后感染等引起皮肤难愈合的研究一直是临床创面修复的难题,对于碱性成纤维细胞生长因子促进皮肤创面愈合的基础研究相对较多,临床应用研究较少。 目的：对碱性成纤维细胞生长因子促进皮肤创面愈合研究的文献资料趋势进行多层次分析,探讨在小儿烧伤创面愈合中的应用疗效。 方法：以电子检索方式对CNKI数据库学术期刊2002-01/2011-12收录有关碱性成纤维细胞生长因子促进皮肤创面愈合研究的文献进行分析,采用检索词为“碱性成纤维细胞生长因子;创面愈合”,运用数据库的分析功能和Excel软件图表的功能分析数据特征。 结果与结论：CNKI数据库学术期刊2002/2011收录碱性成纤维细胞生长因子促进皮肤创面愈合研究的文献共228篇,文献数量处于平稳发展趋势。《中国组织工程研究与临床康复》杂志收录的文献数量最多为26篇。解放军第304医院产出的文献最多。碱性成纤维细胞生长因子促进皮肤创面愈合研究文献的基金资助项目有16项,基金资助项目的文献共76篇,以国家重点基础研究发展计划(973)项目和国家自然科学基金资助项目的文献最多。碱性成纤维细胞生长因子在小儿烧伤创面愈合中应用的文献虽然较少,但实验结果均显示治疗效果较好,有促进小儿Ⅱ度烧伤创面愈合的作用,而且无不良反应出现。     

干细胞治疗皮肤创伤的研究

皮肤创伤愈合是一个复杂的生物学过程,其中慢性难愈性创伤和瘢痕形成目前尚缺乏有效的治疗手段。干细胞是一类具有自我更新和多向分化潜能的细胞类型,内源性的干细胞在创伤愈合中发挥着重要作用,移植的外源性干细胞也能明显促进创面愈合,因此干细胞在治疗皮肤创面愈合中有着广阔的应用前景。本文就干细胞在治疗皮肤创伤中的相关机制及如何提高治疗效果等方面的研究进行简要综述,旨在为后续的研究及临床应用提供参考。     

创面愈合及瘢痕形成中的结缔组织生长因子

背景:创面愈合是外科学研究的热点。结缔组织生长因子参与调节皮肤创面愈合过程并发挥了重要作用。目的:综述结缔组织生长因子在创面中的表达规律及其在瘢痕愈合和创面愈合中的作用。方法:运用计算机检索中国CNKI学术总库(www.cnki.net)、万方数据库、维普中文科技期刊数据库、Springer Link及Pub Med数据库相关文章。以"结缔组织生长因子;瘢痕;创面愈合;再生"为中文检索词;以"CTGF;CCN2;Wound healing;Regeneration"为英文检索词。纳入37篇关于结缔组织生长因子的基础研究及其在创面愈合实验中相关研究进行讨论。结果与结论:结缔组织生长因子在皮肤创面愈合及瘢痕形成过程中呈动态表达。在创伤修复初期,结缔组织生长因子的短暂上调可促进肉芽组织和新生血管形成等加速创面修复过程;在伤口修复和重塑阶段的持续表达可明显促进过度基质的产生、胶原沉积和瘢痕挛缩,导致病理性瘢痕的发生。结缔组织生长因子参与了皮肤创面的愈合过程,其在加速创面愈合和控制瘢痕形成方面可能具有应用前景。结缔组织生长因子作为转化生长因子β的下游产物,除本身的生物学作用外,其介导转化生长因子β的促成纤维细胞增殖、促纤维化、诱导黏附及迁移等作用是其影响创面愈合的作用机制之一。     

生长因子与创面愈合

皮肤创面愈合是一复杂的生物学过程,又是创伤后所引起的病理过程的总称。它包括炎症反应,细胞增殖,创面收缩,胶原代谢等基本过程。创面愈合受多种因素调控,其中多种生长因子在创面愈合过程具有重要作用。通常认为是由进入创面的成纤维细胞增殖、分化和合成分泌,细胞外基质的纤维化,新生血管长入创面的血管化和表皮细胞增生覆盖创面等综合作用的结果。而在愈合过程中产生的生长因子大多对皮     

角质形成细胞来源的胞外囊泡在创面修复中的研究进展

胞外囊泡(EV)是细胞分泌的内含大量生物活性分子的膜性囊泡,作为细胞间通讯的主要媒介,参与调控细胞的生理进程。大量研究证明,EV在创面修复中具有极大潜力,主要通过参与调控创面的急慢性炎症反应、促进细胞增殖、分化、迁移及新生血管生成、调控创面重塑阶段等多方面来促进创面愈合。而角质形成细胞作为皮肤表皮中最主要的细胞,通过分泌EV来与其他皮肤细胞交流,参与皮肤创面愈合的过程。因此,本文对近年来角质形成细胞EV作用于创面修复和再上皮化的研究进展进行综述,为临床创面修复治疗提供一种新的干预手段或方式。     

护创膜对兔创面愈合的影响

目的探讨护创膜对兔创面愈合的影响。方法制做兔背全层创伤模型,分成实验组和对照组,创面分别外用护创膜及无菌凡士林敷料。伤后3、5、7、10、l4、17、21d观察两组创面愈合时间和创面愈合率;并分别取创面组织进行病理组织学检查评估创面的修复质量,对实验组和对照组的创面愈合时间和创面愈合率及修复质量进行观察比较。结果护创膜与凡士林纱布相比能加速创面愈合(P<0.O5),护创膜组在皮肤愈合的组织病理等级评分上优于凡士林纱布组(P<0.05)。结论护创膜促进创面愈合并提高愈合的质量,是创面修复的一种较理想的生物敷料。     

Wound care management: proper protocol differs from athletic trainers' perceptions

As research techniques in wound care management improve, treatment protocols for the care of wounds must also change to ensure safe and optimal healing. In this study, I surveyed current practices of athletic trainers regarding the care of athletic wounds and compared the findings to current literature. I contacted 501 athletic trainers, including all NATA curricular undergraduate directors. Overall response rate was 58%; 78% of the athletic trainers from the curricular schools responded. Wet-to-dry, irrigation, and soaks were the three most common methods used to debride and cleanse a wound. Povidone-iodine (Betadine) and hydrogen peroxide were the two most popular cleansing agents. Conventional gauze was the primary dressing used by 67% of the athletic trainers, while 20% of those surveyed used occlusive dressings. Although povidone-iodine and hydrogen peroxide are commonly used, both are toxic to cells involved in the wound-healing process and delay healing. Research indicates that the best method of cleansing and debriding a wound is to irrigate it with saline. Occlusive dressings have a lower infection rate, are viral barriers, and are associated with faster wound healing and less pain than gauze dressings. Athletic trainers need to assess their wound care protocols so that they give the best possible care to their athletes.     

TGF-beta: a fibrotic factor in wound scarring and a potential target for anti-scarring gene therapy

Hypertrophic scar and keloid are common and difficult to treat diseases in plastic surgery. Results of wound healing research over the past decades have demonstrated that transforming growth factor-beta (TGF-beta) plays an essential role in cutaneous scar formation. In contrast, fetal wounds, which heal without scarring, contain a lower level of TGF-beta than adult wounds. How to translate the discovery of basic scientific research into the clinical treatment of wound scarring has become an important issue to both clinicians and basic researchers. The development of gene therapy techniques offers the potential to genetically modify adult wound healing to a healing process similar to fetal wounds, and thus reduces wound scarring. This article intends to review the roles of TGF-beta in the formation of wound scarring, the possible strategies of antagonizing wound TGF-beta, and our preliminary results of scar gene therapy, which show that wound scarring can be significantly reduced by targeting wound TGF-beta.     

Cell Therapy for Wound Healing

In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.

Graphical Abstract

相似文献   

Comprehensible evaluation of prognostic factors and prediction of wound healing

We analyzed the data of a controlled clinical study of the chronic wound healing acceleration as a result of electrical stimulation. The study involved a conventional conservative treatment, sham treatment, biphasic pulsed current, and direct current electrical stimulation. Data was collected over 10 years and suffices for an analysis with machine learning methods. So far, only a limited number of studies have investigated the wound and patient attributes which affect the chronic wound healing. There is none to our knowledge to include treatment attributes. The aims of our study are to determine effects of the wound, patient and treatment attributes on the wound healing process and to propose a system for prediction of the wound healing rate. First we analyzed which wound and patient attributes play a predominant role in the wound healing process and investigated a possibility to predict the wound healing rate at the beginning of the treatment based on the initial wound, patient and treatment attributes. Later we tried to enhance the wound healing rate prediction accuracy by predicting it after a few weeks of the wound healing follow-up. Using the attribute estimation algorithms ReliefF and RReliefF we obtained a ranking of the prognostic factors which was comprehensible to experts. We used regression and classification trees to build models for prediction of the wound healing rate. The obtained results are encouraging and may form a basis for an expert system for the chronic wound healing rate prediction. If the wound healing rate is known, then the provided information can help to formulate the appropriate treatment decisions and orient resources towards individuals with poor prognosis.     

The role of endothelial dysfunction in the pathogenesis of impaired diabetic wound healing: A novel therapeutic target?

The global burden of diabetes is attributed to its multiple associated complications including impaired wound healing which can ultimately result in amputation. Peripheral vascular disease, infection, neuropathy and abnormal local cellular and cytokine activity are some of the traditionally cited pathological instigators of defective diabetic wound repair. Despite intensive research and subsequent advances in diabetic wound care technology a single treatment with measurable clinical impact has yet to be determined. The phenomenon of endothelial dysfunction as seen in atherosclerosis and recently identified as a characteristic of diabetic vasculature may contribute to impaired cutaneous healing in this group. Indicators of endothelial dysfunction have been demonstrated in diabetic wounds by a number of investigators. Successful results are being obtained with modifiers of endothelial function in the management of cardiovascular disease. We hypothesise that endothelial dysfunction plays a substantial contributory role in the pathogenesis of wound healing impairment of diabetes and holds potential as a target for therapeutic intervention.     

表皮干细胞：治疗难愈性皮肤创面的种子细胞

难愈性皮肤创面是指在期望的时间内不能正常愈合的皮肤组织创面。本文以表皮干细胞（ESC）为靶点,对其在难愈性皮肤创面愈合中的研究和应用进行综述。首先介绍ESC的解剖位置和对创面愈合的调节作用。其次,总结难愈性皮肤创面的特点及共同的病理学机制。最后,归纳ESC在难愈性皮肤创面愈合中的作用：直接修复损伤皮肤组织;作为组织工程学构建人工皮肤的种子细胞;以及其基因修饰治疗用于皮肤创面修复。     

Placenta growth factor in diabetic wound healing: altered expression and therapeutic potential

Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process.     

循环纤维细胞与慢性创面愈合

背景：循环纤维细胞是近些年来在外周血液发现的具有成纤维细胞特性的一种白细胞亚群,由于具有合成多种细胞外基质蛋白、细胞因子以及递呈抗原、收缩创面、促进新生血管形成的能力,因此被认为可以促进创伤的修复。但其促进慢性创面修复的潜在作用研究尚少。 目的：通过文献检索,对循环纤维细胞的生物学特性及其在慢性创面修复中的潜在作用进行文献综述。 方法：分别以“循环纤维细胞、慢性创面、糖尿病足、创面愈合、细胞治疗”和“circulating fibrocytes、An-healing wounds、diabetic foot ulcer、wound healing、cell therapy”为关键词进行检索,CNKI数据库的检索时限为2000至2014年,PubMed数据库的检索时限为1994至2015年,西文生物医学期刊文献数据的检索时限为2000至2015年,检索内容为循环纤维细胞、慢性创面的难愈机制以及细胞治疗在慢性创面愈合中的应用。保留符合纳入标准的54篇文献进行总结分析。 结果与结论：循环纤维细胞因其安全、有效并能较好的发挥促进创面愈合的作用,细胞治疗已开始应用于创面修复。循环纤维细胞是在外周血发现的具有成纤维细胞特性的一个新型白细胞亚群,具有合成多种细胞外基质蛋白、细胞因子以及递呈抗原、收缩创面、促进新生血管形成的能力并在伤后早期进入损伤部位,在创伤修复过程中发挥着积极作用。动物研究证实,应用循环纤维细胞可改善慢性创面尤其是糖尿病慢性创面的修复。   中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程