LED红光对糖尿病大鼠创面愈合的影响

目的探讨LED红光照射对糖尿病大鼠创面愈合的作用及相关机制。 方法将30只4周龄雄性SD大鼠按随机数字表法分为正常创面组、糖尿病创面组、红光治疗糖尿病创面组,每组10只。红光治疗糖尿病创面组及糖尿病创面组大鼠高脂饮食4周,正常创面组大鼠正常饮食。饲养4周后对红光治疗糖尿病创面组及糖尿病创面组大鼠按50 mg/kg的量腹腔注射10 mg/mL的链脲佐菌素(STZ)制作糖尿病大鼠模型,2组大鼠均造模成功。造模成功后在3组大鼠的背部两侧各制造2个1.5 cm×1.5 cm的全层皮肤缺损创面,每2 d对大鼠创面进行酒精消毒1次,红光治疗糖尿病创面组大鼠每次消毒后对创面进行LED红光照射5 min,能量密度为20 J/cm²,另外2组大鼠不进行LED红光照射。在观察第7、10、14、21天,观察红光治疗糖尿病创面组大鼠创面有无出现皮疹、红肿、水疱、烫伤等光照不良反应;肉眼观察3组大鼠创面愈合情况;统计3组大鼠创面愈合率。观察第10天从各组随机取2只大鼠,处死后取背部创面组织,固定后,进行苏木精-伊红染色观察创面新生血管情况及肉芽组织生长情况;采用免疫荧光法检测各组大鼠创面组织中CD34、血管内皮细胞生长因子(VEGF)表达情况。数据比较采用单因素方差分析和LSD-t检验。 结果观察第7、10、14、21天,红光治疗糖尿病创面组大鼠经LED红光照射后皮肤未见皮疹、红肿、水疱、烫伤等光照不良反应。在各个观察时间点,肉眼观察正常创面组及红光治疗糖尿病创面组创面愈合情况均优于糖尿病创面组,且正常创面组创面愈合情况略优于红光治疗糖尿病创面组;观察第7、10、14、21天,正常创面组的创面愈合率分别为(34.62±2.116)%、(53.83±7.92)%、(70.20±5.41)%、(95.65±2.58)%,红光治疗糖尿病创面组创面愈合率分别为(31.76±2.44)%、(50.48±4.54)%、(66.26±11.35)%、(93.96±2.80)%,糖尿病创面组创面愈合率分别为(23.67±4.18)%、(42.71±3.40)%、(53.77±7.74)%、(84.07±4.43)%,3组比较差异均有统计学意义(F＝34.69、10.35、10.32、34.40,P<0.05);观察第7、10、14、21天,正常创面组及红光治疗糖尿病创面组创面愈合率始终高于糖尿病创面组,差异均有统计学意义(P<0.05);观察第7、10天,正常创面组创面愈合率高于红光治疗糖尿病创面组,差异均有统计学意义(t＝2.80、3.26,P<0.05),观察第14、21天,正常创面组创面愈合率仍高于红光治疗糖尿病创面组,但差异均无统计学意义(t＝1.16、1.40,P>0.05)。观察第10天,创面组织苏木精-伊红染色显示,正常创面组内含大量新生毛细血管,肉芽组织内胶原及细胞排列紧密有序;红光治疗糖尿病创面组见较多新生毛细血管,肉芽组织内胶原及细胞较多,但少于正常创面组;而糖尿病创面组新生血管最少,肉芽组织内细胞及胶原稀疏。免疫荧光法检测创面组织中CD34、VEGF表达情况可见,正常创面组CD34、VEGF表达高于红光治疗糖尿病创面组,而红光治疗糖尿病创面组表达高于糖尿病创面组。 结论LED红光可促进糖尿病大鼠创面组织中CD34、VEGF表达,促进血管新生,进而促进创面愈合。     

神经生长因子在糖尿病足创面组织中表达相关性的研究进展

动物实验研究证实神经生长因子（NGF）促进创面组织血管生成、血管内皮细胞再生,促进缺血创面的愈合及糖尿病创面的愈合。通过NGF在糖尿病创面表达改变的研究,有助于NGF促进糖尿病创面愈合机制的探讨,为糖尿病足创面愈合提供新的理论依据。     

甲壳素麻油蜂蜡膏促进糖尿病足创面愈合的研究进展

慢性创面（包括糖尿病足溃疡）合适敷料的应用,创造良好的伤口愈合环境,是临床工作面临的课题。甲壳素、麻油、蜂蜡能有效促进体表创面的愈合,甲壳素麻油蜂蜡膏更能有效促进创面的愈合,为临床敷料的应用提供更多的选择。     

负压创面治疗技术在糖尿病足溃疡中的应用及护理

目的 探讨负压创面治疗技术（NPWT）在治疗糖尿病足溃疡中的应用及护理要点.方法 2012年8月至2013年4月对9例糖尿病足wagner分级为3～4级的糖尿病足患者在糖尿病足病灶清除术后使用NPWT治疗,2～3周后植皮或换药,观察创面愈合效果及加强术后负压引流的护理、伤口的护理及基础护理.结果 应用NPWT治疗糖尿病足溃疡创面,术后创面肉芽组织生长良好,骨外露基本覆盖,为后期治疗创造良好治疗条件,9例糖尿病足患者的溃疡全部愈合.结论 应用NPWT、术后负压引流的护理、伤口的护理及基础护理是保障NPWT治疗糖尿病足的关键环节.     

皮肤发育相关的miRNAs及其在糖尿病创面愈合中的作用*

微小核糖核酸（microRNA/miRNA）作为一类进化上保守的非编码小分子RNA,参与基因转录后的表达与 调控,其表达模式有一定的时间性和空间性,体现在不同的miRNAs在不同组织、不同发育阶段的表达水平差异。 某些miRNAs能够促进创面愈合,在创面愈合的炎症期抑制炎性介质的表达;某些miRNAs能够促进增生期创面 细胞的增殖、迁移,有利于创面的快速修复;在创面重塑期,某些miRNAs又能够通过抑制无痕愈合信号通路的 相关蛋白质来促使瘢痕修复。糖尿病创面通常伴随糖尿病周围神经病变、糖尿病血管病变和感染。部分miRNAs 通过调控特定基因的表达水平,激活或抑制不同且特定的信号通路,一定程度上促进了糖尿病创面的愈合。本文 主要综述了miRNA在创面愈合过程不同阶段的调控研究进展,以及miRNAs促进、抑制糖尿病创面愈合的机制, 以期为后续研究开拓新的思路。     

P物质对成纤维细胞Rac-1/JNK通路及糖尿病创面愈合的影响

目的 研究外源性P物质(SP)对成纤维细胞迁移的影响及糖尿病小鼠创面愈合的作用.方法 利用Transwell细胞迁移试验、划痕试验检测SP对小鼠成纤维细胞迁移能力的影响.筛选建模成功的糖尿病小鼠20只,随机分为对照组和SP组.分别于皮肤损伤后4、8、12、16、20d,观察创面愈合情况并计算创面愈合率,并于7、14、2...     

HO1工程化无细胞提取液联合石墨烯远红外光促糖尿病溃疡修复的疗效及机制

目的 探讨HO1工程化无细胞提取液(CE)联合石墨烯远红外光(FIR)在糖尿病溃疡创面修复中的疗效及机制。方法 将40只6～8周龄雄性C57BL/6小鼠建立正常创面模型(对照组,n=8)及糖尿病溃疡模型(n=32),其中将糖尿病溃疡模型小鼠随机分为糖尿病组、^HO1BMSCs-CE组、FIR组、联合组。构建过表达血红素氧合酶1(HO1)的骨髓间充质干细胞(BMSCs),获取工程化富含HO1蛋白的无细胞提取液(^HO1BMSCs-CE),运用Western blot、ELISA、RT-PCR、Masson染色、免疫组化等检测各组创面愈合率、组织修复情况、创面氧化应激及炎症水平等。结果 Western blot及ELISA检测结果显示,^HO1BMSCs-CE中HO1、表皮生长因子(EGF)、转化生长因子-β(TGF-β)表达水平显著高于BMSCs-CE(P<0.05)。治疗后第5、11天,联合组的创面愈合率均显著高于^HO1BMSCs-CE组和FIR组(P<0.05)。与^HO1     

负压封闭引流技术与常规创面敷料换药治疗糖尿病患者四肢创面的比较

目的比较负压封闭引流( VSD)技术和常规敷料换药在糖尿病患者四肢慢性创面治疗中的应用效果。方法回顾性分析2004年3月—2014年3月武汉大学中南医院显微骨科收治的464例伴有四肢开放性伤口不愈合的糖尿病患者的临床资料,其中应用VSD技术治疗240例( VSD组),应用常规敷料覆盖创面换药治疗224例(传统治疗组)。观察2组患者创面愈合时间、创面愈合率、治疗费用及治疗后的复发率,采用t检验和字2检验对观察结果进行对比分析。结果 VSD组240例,创面愈合234例,创面愈合率97.5%,创面愈合时间12.6~24.2 d,平均(16.4依1.5)d;6例创面不愈合的患者二期行局部皮瓣转位术后治愈。患者住院期间所产生的费用为7500~12000元,平均为(9200.0依100.2)元。传统治疗组224例,创面愈合192例,创面愈合率85.7%;创面愈合时间22.3~36.4 d,平均(30.6依3.5)d。32例创面不愈合的患者二期行局部皮瓣转位术后治愈。患者住院期间所产生的费用为9500~14000元,平均为(12000.0依182.6)元。 VSD组创面愈合率明显高于传统治疗组(字2=25.78,P<0.05);在创面愈合患者中,VSD组创面愈合时间及治疗费用均明显低于传统治疗组,差异均有统计学意义(t时间=56.80,t费用=86.10,P值均<0.05)。本组464例患者均获随访,随访时间为3~5个月,平均4个月。随访期间所有患者均无变态反应发生。在创面愈合患者中,VSD组患者创面复发3例,复发率1.3%(3/234),传统治疗组创面复发9例、复发率4.7%(9/192),两组比较差异有统计学意义(字2=4.51,P<0.05)。结论运用VSD技术处理糖尿病患者的四肢慢性创面,可提高创面愈合率、缩短住院时间、节省住院费用、降低复发率,与传统换药相比优势明显。     

贝复济在糖尿病下肢血管病变治疗中的应用研究

目的 探讨贝复济(重组牛碱性成纤维细胞生长因子)对糖尿病下肢血管病变的治疗效果.方法 选择住院诊治的糖尿病足患者32例,依据治疗方法不同随机分为贝复济组(降血糖 抗感染 贝复济局部换药)16例,对照组(降血糖 抗感染)16例.对比两组患者治愈率、创面愈合时间及过敏、不良反应发生情况.结果 贝复济组治愈率(93.75%)明显高于对照组(62.5%,P＜0.05);贝复济组创面愈合时间(29.34±1.46)d 明显比对照组(38.23±2.87)d 缩短(P＜0.05).两组均无过敏及其他不良反应.结论 在糖尿病下肢血管病变治疗中应用贝复济,可缩短创面愈合时间,提高治愈率.     

石香膏干预糖尿病溃疡创面模型大鼠创面组织晚期糖基化终产物及其受体与内皮型一氧化氮合成酶表达的变化

背景:糖尿病溃疡作为糖尿病的常见并发症之一,其低愈合率和高截肢率已严重危害人类健康,尽管目前多种中医外用膏药已证实能促进创面愈合,但其发挥作用的分子机制尚未明确.目的:探讨石香膏治疗糖尿病溃疡创面的可能作用机制.方法:将40只清洁级雄性SD大鼠随机分正常对照组、糖尿病溃疡组、细胞生长因子组、石香膏组,每组10只.除正常...     

Cancer is a functional repair tissue

When a wound occurs, growth and repair genes (GR genes, such as oncogenes, proto-oncogenes, etc.) in surrounding cells are activated and secretion of growth and repair factors (GR factors, such as growth, stem cell, and stimulating factors, etc.) is induced to heal the wound. However, if the wound is persistent due to chronic physical (radiation, electromagnetic field, trauma, particles, etc.), chemical (carcinogens, toxic chemicals, heavy metals etc.) or biological (aging, free radicals, inflammation, nutrient deficiency, bacteria and virus infections, stress, etc.) damage, amplification of GR gene activation in surrounding cells may lead to a clinical cancer. Based on the commonalities between cancer and wound healing, a new hypothesis of cancer is presented: malignancies are not passive mutated useless masses; rather, they are functional tissues produced by GR gene activation to secrete GR factors in an effort to heal persistent wounds in the body. Based on the hypothesis, current cancer treatments aimed at killing cancer cells only may be misguided. The logical extension of the hypothesis is that cancer treatment focused on wound healing by limiting causes of persistent wounds, providing repair cells, GR factors, and substrates required by repair cells may yield more fruitful results than treatments focused on killing cancer cells alone. Spontaneous regressions of cancer, although rare, may be successful examples of serendipitous spontaneous wound healing. Standard therapies aimed at killing cancer cells, should be limited to adjuvant status for limiting symptoms or buying time for completion of the wound healing process. Attempts to destroy cancer cells without healing underlying persistent wounds will allow for eventual recurrence.     

Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing

Nonhealing wounds of the lower equine limb represent a challenging model. The platelet is a natural source of a myriad of growth factors and cytokines that promote wound healing. This study evaluates the potential of platelet derived factors to enhance wound healing in the lower equine limb. Platelets were isolated from horse blood and activated with thrombin, a process known to induce growth factor release. This produced a platelet gel composed of platelet-rich plasma (PRP). To test this all-natural wound healant, 2.5-cm(2) full thickness cutaneous wounds were created below the knee and hock of a thoroughbred horse. Wounds were treated with PRP gel or left untreated. Sequential wound biopsies collected at Days 7, 36, and 79 postwounding permitted comparison of the temporal expression of differentiation markers and wound repair. To test the hypothesis that wounds treated with PRP gel exhibit more rapid epithelial differentiation and enhanced organization of dermal collagen compared to controls, tissues were stained for cytokeratin 10, a suprabasal differentiation marker, and the reestablishment of collagen was evaluated by trichrome staining. PRP gel-treated wounds at Day 7 expressed intense cytokeratin 10 staining near the wound junction in suprabasal epidermal layers, while staining in control tissues was less intense and restricted to apical epidermal layers distal to the wound junction. By Day 79, the staining was equal in both groups. However, PRP gel-treated wounds at Day 79 contained abundant, dense collagen bundles oriented parallel to each other and to the overlying epithelium, whereas control tissues contained fewer collagen fibers that were oriented randomly. Thus, treatment of wounds with PRP gel induced accelerated epithelial differentiation and produced tissue with organized, interlocking collagen bundles. This study reveals that this novel all-natural wound healant induced wound repair in injuries previously deemed untreatable.     

Regulation of scar formation by vascular endothelial growth factor

Vascular endothelial growth factor (VEGF-A) is known for its effects on endothelial cells and as a positive mediator of angiogenesis. VEGF is thought to promote repair of cutaneous wounds due to its proangiogenic properties, but its ability to regulate other aspects of wound repair, such as the generation of scar tissue, has not been studied well. We examined the role of VEGF in scar tissue production using models of scarless and fibrotic repair. Scarless fetal wounds had lower levels of VEGF and were less vascular than fibrotic fetal wounds, and the scarless phenotype could be converted to a scar-forming phenotype by adding exogenous VEGF. Similarly, neutralization of VEGF reduced vascularity and decreased scar formation in adult wounds. These results show that VEGF levels have a strong influence on scar tissue formation. Our data suggest that VEGF may not simply function as a mediator of wound angiogenesis, but instead may play a more diverse role in the wound repair process.     

Diminished type III collagen promotes myofibroblast differentiation and increases scar deposition in cutaneous wound healing

The repair of cutaneous wounds in the postnatal animal is associated with the development of scar tissue. Directing cell activities to efficiently heal wounds while minimizing the development of scar tissue is a major goal of wound management and the focus of intensive research efforts. Type III collagen (Col3), expressed in early granulation tissue, has been proposed to play a prominent role in cutaneous wound repair, although little is known about its role in this process. To establish the role of Col3 in cutaneous wound repair, we examined the healing of excisional wounds in a previously described murine model of Col3 deficiency. Col3 deficiency (Col3+/-) in aged mice resulted in accelerated wound closure with increased wound contraction. In addition, Col3-deficient mice had increased myofibroblast density in the wound granulation tissue as evidenced by an increased expression of the myofibroblast marker, α-smooth muscle actin. In vitro, dermal fibroblasts obtained from Col3-deficient embryos (Col3+/- and -/-) were more efficient at collagen gel contraction and also displayed increased myofibroblast differentiation compared to those harvested from wild-type (Col3+/+) embryos. Finally, wounds from Col3-deficient mice also had significantly more scar tissue area on day 21 post-wounding compared to wild-type mice. The effect of Col3 expression on myofibroblast differentiation and scar formation in this model suggests a previously undefined role for this ECM protein in tissue regeneration and repair.     

Regulation of wound healing by growth factors and cytokines

Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.     

Scar‐free cutaneous wound healing in the leopard gecko,Eublepharis macularius

Cutaneous wounds heal with two possible outcomes: scarification or near‐perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue‐level events characterising wounds that spontaneously heal scar‐free, particularly in non‐foetal amniotes. Here, a spatiotemporal investigation of scar‐free cutaneous wound healing following full‐thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell‐rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar‐free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar‐free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar‐free wound healing the newly formed blood vessels are typically perivascular cell‐supported. Immunohistochemistry revealed widespread expression of both the pro‐angiogenic factor vascular endothelial growth factor A and the anti‐angiogenic factor thrombospondin‐1 within the healing wound. It was found that scar‐free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar‐free wound healing.     

Gene therapy of scarring: a lesson learned from fetal scarless wound healing.

Cutaneous wounding in adult humans and higher vertebrate animals results in scar formation. In contrast, both human and animal fetuses, at early gestational ages, exhibit skin wound healing without scarring. This distinction suggests that the repair of adult wounds by skin regeneration, rather than by fibrosis, may be achieved if adult wounds can be modified to mimic the healing process of fetal wounds. The development of gene therapy offers the possibility to specifically enhance or block the gene expression of cytokines and extracellular molecules, and thus convert adult wound healing into a healing process more similar to tissue regeneration. This article reviews the characteristics of fetal wound repair focusing on cytokine profiles and the inflammatory response to dermal injury. Also included are new developments in gene transfer techniques as well as their application in wound healing. Finally, the authors propose possible strategies of wound gene therapy, to reduce wound scarring and to promote tissue regeneration.     

Diverse and potent activities of HGF/SF in skin wound repair

Genetic studies in the mouse have highlighted essential roles for several growth factors in skin repair and have offered a rationale for their use in therapy. The present study shows that the plasminogen-related growth factor HGF/SF (hepatocyte growth factor/scatter factor) promotes wound repair in homozygous diabetic db/db mice by recruiting neutrophils, monocytes, and mast cells to the wound; by promoting the migration of endothelial cells to the injured area; and by enhancing keratinocyte migration and proliferation. As a result, granulation tissue formation, wound angiogenesis, and re-epithelialization are all increased. The results demonstrate that HGF/SF affects and sustains all key cellular processes responsible for wound repair and point to a unique potential of this molecule for the therapy of chronic skin wounds.     

Could chronic wounds not heal due to too low local copper levels?

Copper is an essential trace element involved in numerous human physiological and metabolic processes. It plays a key role in many of the processes that together comprise wound healing, including induction of endothelial growth factor, angiogenesis and expression and stabilization of extracellular skin proteins. We hypothesize that in individuals with diabetic ulcers, decubitus, peripheral vascular, or other wounds which might have compromised circulation to the wound site, that part of the incapacity of the wounds to heal is due to low local copper levels. Contamination of wounds is also an important factor causing impaired wound healing. Importantly, copper has potent broad biocidal properties. In contrast, the risk of adverse skin reactions due to exposure to copper is extremely low. We thus hypothesize that introducing copper into wound dressings would not only reduce the risk of wound and dressing contamination, as silver does but, more importantly, would stimulate faster wound repair directly. This would be done by the release of copper from the wound dressings directly into the wound site inducing angiogenesis and skin regeneration.     

Accelerated wound closure in mice deficient for interleukin-10

The impact of the local inflammatory response on the process of wound healing has been debated for decades. In particular, the question whether infiltrating macrophages and granulocytes promote or impede tissue repair has received much attention. In the present study, we show that wound healing is accelerated in mice deficient for the anti-inflammatory cytokine interleukin (IL)-10. IL-10-/- mice closed excisional wounds significantly earlier compared with IL-10-competent control littermates. This effect was attributable to accelerated epithelialization as well as enhanced contraction of the wound tissue in the mutant animals. Increased alpha-smooth muscle actin expression in IL-10-deficient mice suggests that augmented myofibroblast differentiation is responsible for the enhanced contraction of wounds in mutant mice. The number of macrophages infiltrating the wound tissue was significantly increased in IL-10-/- mice compared with control littermates suggesting that this cell type mediates the accelerated tissue repair. These results show for the first time that IL-10 can impede wound repair.