MiRNA 与皮肤伤口愈合

MiRNA是真核生物体内约由22个核苷酸组成的内源性非编码单链RNA,可调节基因转录。它通过其5’非翻译区(UTR)与目标mRNA的3’端非翻译区相结合,从而抑制后者的转录后翻译和降解,进而调节一系列生物学过程,包括生物体生长、发育和疾病等。研究表明,miRNA在干细胞分化、肿瘤形成、血管发生、内耳形成等过程中均发挥重要作用,已成为调节生物学过程的核心因子。伤口愈合是一个与多种类型细胞、细胞因子及细胞外基质相关的过程,它受机体多种因素紧密调控。伤口愈合过程一般被分为三个阶段:炎症反应期,肉芽生长期和组织重建期。已有大量证据证实miRNA在皮肤创伤愈合过程中发挥重要作用,并且miRNA在不同的愈合阶段发挥不同的作用。本文就miRNA在皮肤形态、胎儿无痕愈合及成人伤口愈合各环节中的作用做一综述。     

Notch与相关调控信号的相互作用在伤口愈合中的调控

皮肤是哺乳动物最重要的组织之一。当皮肤受损时,受损组织通过系列伤口愈合反应的生理和心理作用被修复,实现组织再生。再生反应主要发生在胚胎发育早期,伤口自愈能力随着机体的成熟而减弱;并且哺乳动物的组织重塑过程较为复杂,在不正确的信号引导下,可能引起并发症而导致创面愈合异常。研究表明,伤口微环境的稳态和信号分子的辅助作用是愈合的重要因素。Notch作为重要的信号通路,参与调控上皮巨噬细胞募集和血管内皮细胞再生等伤口愈合阶段。Wnt信号促进伤口表皮干细胞的增殖和血管网络结构的形成。Hedgehog信号驱动伤口处毛囊发育及其周围组织再生,TGF-β信号有助于愈合时多细胞层形成和瘢痕减少。本文重点阐述Notch信号通路以及Notch与相关信号分子互作在伤口愈合中的调控作用,旨在总结信号分子在组织工程研究方面的最新进展,分析伤口微环境的信号互作机制,为长时间伤口愈合和过度伤口愈合的治疗提供理论依据。     

近红外线照射与局部氧疗对伤口愈合作用的实验研究

目的:研究近红外照射与局部氧疗相结合对伤口愈合的作用及机理.方法:以新西兰种兔为研究对象,建立创伤模型,并将创伤兔随机分为四组,分别对伤口施加近红外照射、局部氧疗、近红外照射 局部氧疗三种治疗,而对照组不施加任何干预,观察伤口愈合情况30天,记录各组伤口愈合数目和愈合天数并计算平均愈合时间.结果:结合治疗组(即近红外照射 局部氧疗组)的20个伤口全部愈合.平均愈合天数是(20.2±2.1)天,分别与红外线照射组、局部氧疗组、对照组存在显著性差异.结论:近红外照射与局部氧疗相结合能促进伤口愈合,是一种新的治疗创伤的方式.     

火器伤合并海水浸泡后对大鼠伤口愈合的影响

目的制造火器伤合并海水浸泡后的动物愈合模型,观察火器伤合并海水浸泡后对伤口愈合过程的影响。方法20只雄性Wistar大鼠随机分为2组：对照组（n=10）及实验组（n=10）。对照组为单纯火器伤。实验组（海水浸泡组）为单纯火器伤后合并海水浸泡30 min。检测愈合过程中2组动物体重增加量变化、面积变化,并对已愈伤口组织行病理学检查。结果实验组伤口愈合时间为16-20 d（17.7±1.3）d,对照组为14-17 d（15.8±0.6）d。对照组动物体重平均增加量显著高于实验组。实验组已愈合伤口组织中存在特殊的病理学变化。     

芦荟汁对小鼠腹部伤口愈合情况影响的研究

目的:本课题主要研究芦荟汁对小鼠腹部伤口愈合情况影响。方法:选择20只成年小鼠为研究对象并随机分为2组。分别采用0.9%生理盐水和芦荟鲜汁对两组进行涂擦小鼠伤口,观察小鼠在给药后一周伤口愈合情况。结果:与对照组比较,实验组小鼠的伤口愈合情况明显好转:有效率比较(p0.05)。结论:芦荟汁对小鼠腹部伤口愈合具有促进作用。     

静电纺丝用作难愈合伤口敷料的研究进展

静电纺丝伤口敷料作为一种新型功能性敷料,具有较大的比表面积、可调控的孔隙率和良好的生物性能,既有益于细胞呼吸,又 可抑制细菌感染伤口,并能促进细胞增殖和加速创面愈合,是未来伤口敷料研发领域发展的新方向。介绍静电纺丝纳米纤维的原理、特点, 重点阐述各类聚合物、生物活性物质在静电纺丝伤口敷料制备中的应用进展。     

恒磁场对伤口愈合的影响

目的:通过平行对照实验,探讨恒磁场对不同种类手术后患者伤口愈合的影响.方法:征集志愿者260例,结合手术种类进行随机分组.对照组常规拆线、普通敷贴,磁场组采用0.2T恒磁敷贴.1月后,对两组问以及磁场组不同手术种类的创伤愈合情况进行评价.结果:恒磁场能提高术后的伤口愈合速度和质量(P<0.01),不同手术种类的患者其疗效之间的差异没有显著性意义(P>0.01).结论:恒磁场在临床术后伤口护理中具有适应症广、使用方便的特点,为临床上磁疗的应用提供了一种新的思路.     

海参胶原低聚肽对糖尿病小鼠术后伤口愈合的促进作用

目的：观察海参胶原低聚肽是否具有促进db/db 2型糖尿病小鼠术后伤口愈合的作用。 方法：取90只10w龄的db/db小鼠分为5组,包括模型对照组乳清蛋白组和3个海参胶原肽组（从低到高分别为0.25、0.50、1.00 g/kg·BW）,每组18只。另设一组同周龄、性别的db/m小鼠18只作为正常对照组。模型对照组和正常对照组使用溶剂（蒸馏水）灌胃。进行背部切口手术后开始干预,分别于术后第4、7、14d分批处死动物,每组每次处死6只。术后观察不同时期伤口愈合情况,测定血清生化指标、皮肤切口抗张力强度以及进行皮肤组织HE染色。结果：与模型对照组相比,海参胶原肽剂量组小鼠血清IL-8水平降低,IL-10水平升高,NO水平升高,伤口抗张力强度提升,伤口愈合较好。结论：海参胶原低聚肽能够改善糖尿病小鼠术后营养状况,促进伤口愈合。     

基于"湿性愈合"理论的新型敷料在糖尿病足溃疡创面处理中的应用

目的:观察基于"湿性愈合"理论的新型敷料用于糖尿病足溃疡创面的处理的治疗效果。方法:首先评估糖尿病足溃疡创面,然后根据不同情况采用不同新型敷料,应用湿性伤口愈合理论对48例糖尿病足溃疡的患者进行临床研究,选取48例传统方法处理的同类患者作为对照。结果:结果显示湿性愈合组患者出院时的创面愈合率较对照组明显提高,治疗周期明显缩短(P<0.05),换药次数明显减少(P<0.05)。结论:基于"湿性愈合"理论的新型敷料在糖尿病足溃疡创面的处理中取得了良好效果,值得进一步研究与应用。     

PDGF在大鼠断层供皮区创面愈合过程中表达变化的研究

实验研究已经证明Ｐｌａｔｅｌｅｔ－ｄｅｒｉｖｅｄｇｒｏｗｔｈｆａｃｔｏｒ（ＰＤＧＦ）能够促进各种类型的伤口愈合,然而在伤口愈合过程中内源性ＰＤＧＦ表达变化的研究却少有报道,为探讨ＰＤＧＦ对伤口愈合的影响,我们应用原位杂交、斑点杂交技术观察了内源性ＰＤＧＦ在大鼠创面愈合过程中的表达变化,结果发现：在创面愈合过程中,肉芽组织中的成纤维细胞,毛细血管内皮细胞及创缘真皮内的毛囊上皮细胞均能表达ＰＤＧＦ－ＢＢ基因,在伤后６天,组织修复的高峰期,ＰＤＧＦ－ＢＢ基因表达达到最强,伤后１２天,伤口完全上皮化,ＰＤＧＦ的基因表达也恢复正常,说明ＰＤＧＦ的基因表达和伤口愈合时间有密切的关系。提示ＰＤＧＦ在创面愈合过程中可能起着重要的调控作用。     

Tissue transglutaminase in normal and abnormal wound healing: Review article

Summary. A complex series of events involving inflammation, cell migration and proliferation, ECM stabilisation and remodelling, neovascularisation and apoptosis are crucial to the tissue response to injury. Wound healing involves the dynamic interactions of multiple cells types with components of the extracellular matrix (ECM) and growth factors. Impaired wound healing as a consequence of aging, injury or disease may lead to serious disabilities and poor quality of life. Abnormal wound healing may also lead to inflammatory and fibrotic conditions (such as renal and pulmonary fibrosis). Therefore identification of the molecular events underlying wound repair is essential to develop new effective treatments in support to patients and the wound care sector.Recent advances in the understating of the physiological functions of tissue transglutaminase a multi functional protein cross-linking enzyme which stabilises tissues have demonstrated that its biological activities interrelate with wound healing phases at multiple levels. This review describes our view of the function of tissue transglutaminase in wound repair under normal and pathological situations and highlights its potential as a strategic therapeutic target in the development of new treatments to improve wound healing and prevent scarring.     

The emerging roles of neutrophil extracellular traps in wound healing

Delayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.Subject terms: Mechanisms of disease, Experimental models of disease     

A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure

A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes, which can be used to deliver novel insights into the process of wound healing, such as geometry related influences, as well as the influence of coupling between the various existing subprocesses on the actual healing behavior. The model confirms the clinical observation that epidermal closure proceeds by a crawling and climbing mechanism at the early stages, and by a stratification process in layers parallel to the skin surface at the later stages. The local epidermal oxygen content may play an important role here. The model can also be used to investigate the influence of local injection of hormones that stimulate partial processes occurring during wound healing. These insights can be used to improve wound healing treatments.     

Laminar shear stress induces the expression of aquaporin 1 in endothelial cells involved in wound healing

Laminar shear stress (LSS) due to blood flow contributes to the maintenance of endothelial health by multiple mechanisms including promotion of wound healing. The present study examined the hypothesis that the induction of water channel aquaporin 1 (AQP1) expression by LSS might be functionally associated with endothelial wound healing. When human umbilical vein endothelial cells were exposed to LSS at 12 dyn cm^?2 for 24 h, significant increases in AQP1 expression were observed at the mRNA and protein levels as compared with static control. In the in vitro scratch wound healing assay, LSS treatments before and after wound creation enhanced endothelial wound healing and this effect was significantly attenuated by selective suppression of AQP1 expression using small interfering RNA. Ectopic expression of AQP1 enhanced wound healing in the absence of LSS. This study demonstrated that LSS stimulates the endothelial expression of AQP1 that plays a role in wound healing.     

Macrophage Dynamics in Diabetic Wound Dealing

Wound healing in diabetes is a complex process, characterised by a chronic inflammation phase. The exact mechanism by which this occurs is not fully understood, and whilst several treatments for healing diabetic wounds exist, very little research has been conducted towards the causes of the extended inflammation phase. We describe a mathematical model which offers a possible explanation for diabetic wound healing in terms of the distribution of macrophage phenotypes being altered in the diabetic patient compared to normal wound repair. As a consequence of this, we put forward a suggestion for treatment based on rectifying the macrophage phenotype imbalance.     

Activin B promotes epithelial wound healing in vivo through RhoA-JNK signaling pathway

Background

Activin B has been reported to promote the proliferation and migration of keratinocytes in vitro via the RhoA-JNK signaling pathway, whereas its in vivo role and mechanism in wound healing process has not yet been elucidated.

Principal Findings

In this study, we explored the potential mechanism by which activin B induces epithelial wound healing in mice. Recombinant lentiviral plasmids, with RhoA (N19) and RhoA (L63) were used to infect wounded KM mice. The wound healing process was monitored after different treatments. Activin B-induced cell proliferation on the wounded skin was visualized by electron microscopy and analyzed by 5′-bromodeoxyuridine (BrdU) incorporation assay. Protein expression of p-JNK or p-cJun was determined by immunohistochemical staining and immunoblotting analysis. Activin B efficiently stimulated the proliferation of keratinocytes and hair follicle cells at the wound area and promoted wound closure. RhoA positively regulated activin B-induced wound healing by up-regulating the expression of p-JNK and p-cJun. Moreover, suppression of RhoA activation delayed activin B-induced wound healing, while JNK inhibition recapitulated phenotypes of RhoA inhibition on wound healing.

Conclusion

These results demonstrate that activin B promotes epithelial wound closure in vivo through the RhoA-Rock-JNK-cJun signaling pathway, providing novel insight into the essential role of activin B in the therapy of wound repair.     

Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats

Inflammation is a crucial step for the wound healing process. The effect of linoleic and oleic acids on the inflammatory response of the skin during the healing process and on the release of pro-inflammatory cytokines by rat neutrophils in vitro was investigated. A wound in the dorsal surface of adult rats was performed and fatty acids were then topically administered. Both oleic and linoleic acids increased the wound healing tissue mass. The total protein and DNA contents of the wounds were increased by the treatment with linoleic acid. The treatments with oleic and linoleic acids did not affect vascular permeability. However, the number of neutrophils in the wounded area and air pouches was increased and the thickness of the necrotic cell layer edge around the wound was decreased. A dose-dependent increase in vascular endothelial growth factor-alpha (VEGF-alpha) and interleukin-1beta (IL-1beta) by neutrophils incubated in the presence of oleic and linoleic acid was observed. Oleic acid was able to stimulate also the production of cytokine-induced neutrophil chemoattractant in inflammation 2 alpha/beta (CINC-2alpha/beta). This pro-inflammatory effect of oleic and linoleic acids may speed up the wound healing process.     

壳聚糖-三聚磷酸钠纳米粒对于肝组织严重出血模型的止血效果

目的:建立SD大鼠肝脏严重出血模型,考察壳聚糖-三聚磷酸钠(TPP)纳米粒的止血效果对于实质性器官严重出血的止血效果。方法:24只SD大鼠各分3组,每组8只,分为阴性对照组、壳聚糖-TPP组(NP组)和正常组,其中阴性对照组和NP组的大鼠建立肝脏严重出血模型。NP组,将壳聚糖-TPP纳米粒喷射到伤口,直至将整个伤口覆盖。阴性对照组,不使用任何止血材料处理创面。术后15天,用SEM和TEM观察NP组和阴性对照组的肝组织的微观结构。结果:通过组织学检查发现壳聚糖-TPP纳米粒在治疗严重伤口时能加速肉芽和大量胶原蛋白的生成,这正是伤口愈合初期的标志。结论:壳聚糖-TPP纳米粒对于严重出血的实质器官可发挥优良的止血性能,并能促使伤口愈合。     

Anti‐aging pharmacology in cutaneous wound healing: effects of metformin,resveratrol, and rapamycin by local application

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate‐activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age‐related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti‐aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR‐based anti‐aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.