促黑素在创面愈合过程作用的研究进展

促黑素(melanocyte-stimulating hormones, MSH)和其它的黑色素主要是由垂体中央部前阿黑皮素(POMC)衍生的内源性的多肽,也可产生于机体的其它组织,通过结合五种黑色素受体而产生生理学效应,包括抗炎症反应、抗微生物、降脂、抑制瘢痕形成等。本文主要是对MSH的分类及生成路径和在创面愈合过程的抗脂、抗瘢痕、抗微生物和抗炎效应进行了综述,并指出研究MSH对参与伤口修复的干细胞的迁移、增殖和分化的调控作用及分子机制,将更好地揭示干细胞参与创面修复的分子机制,为再生医学研究提供更多的理论支持。     

创面愈合过程中EGFr基因表达的研究

应用原位分子杂交技术观测了大鼠创面愈合过程中表皮生长因于受体(Epidermalgrowth factor receptor,EGFr)的信使核糖核酸(mRNA)表达的变化.结果表明:伤后4天EGFrmRNA即有明显的表达,以后逐渐减弱,伤后16天EGFr mRNA已无明显表达.对EGFr基因表达的作用和机理进行了讨论.     

创面愈合过程中C-myc基因表达变化研究

应用原位杂交技术观测了大鼠创面愈合过程中Ｃ－ｍｙｃ基因表达变化。结果表明：在创面愈合过程中,Ｃ－ｍｙｃ基因有规律表达,以伤后第表达最强。对Ｃ－ｍｙｃ基因表达的作用和机理引起了讨论。Ｃ－ｍｙｃ基因表达参与了创面愈合过程     

rh-GH在促进大鼠创面愈合中的作用研究

目的:通过在大鼠背部创面周围局部注射rh-GH(重组人生长激素,Recombinant Human Growth Hormone)来调控创面局部GH(生长激素,Growth Factor)水平,观察GH在创面愈合中的作用,并对其可能机制进行进一步研究。方法:在SD大鼠背部制作创面,创周定期注射不同浓度rh-GH,观察并分析创面愈合速度差异;选取rh-GH的最适浓度进行创周注射并定期取材,以Western-Blot检测创周组织中GH蛋白水平,并以RT-PCR检测创周组织中EGF(表皮生长因子,Epidermal Growth Factor)、FGF(成纤维细胞生长因子,Fibroblast Growth Factor)、VEGF(血管内皮细胞生长因子,Vascular Endothelial Growth Factor)的表达变化。结果:三个注射不同剂量rh-Gh的实验组大鼠创面平均愈合时间由快至慢依次为16.5±1.5天、17.1±2.9天、18.5±1.5天,与注射生理盐水的对照组平均愈合时间21.7±2.3天相比均明显增快,差异有统计学意义(P0.05)。创缘组织中GH的Western-Blot结果显示对照组GH水平在创面形成初期升高,但伤后4天开始GH表达水平即逐渐下降,而rh-GH注射组的GH水平在创面形成后逐渐升高,并维持GH在高表达水平。检测创周组织中EGF、FGF、VEGF的RNA转录水平,PCR结果显示实验组各生长因子的基因转录水平在伤后2天起即明显高于对照组,差异有统计学意义(P0.05)。结论:1.创伤初期创面周围组织中GH表达水平呈现一过性升高然后逐渐下降的过程;2.创面周围注射rh-GH可以提高组织中GH水平,并减少创面愈合时间;3.GH可以提高皮肤组织中EGF、FGF、VEGF水平,间接促进创面上皮化,加快创面愈合。     

炎症反应促进肿瘤的侵袭和转移的研究进展

恶性肿瘤严重威胁人类健康,其侵袭和转移是肿瘤患者死亡的重要原因。大量研究表明,肿瘤微环境对肿瘤细胞的侵袭和转移有着重要的作用。肿瘤细胞在肿瘤微环境中会受到多种因素的影响,其中炎症反应产生的多种炎症细胞、细胞因子等会为肿瘤细胞的恶性转化提供有利条件。     

腺苷及其受体在皮肤创面愈合与纤维化中的作用

皮肤的急慢性创面在临床上较常见,个体差异性大,且慢性创面治疗较为棘手;此外,皮肤纤维化疾病日渐增多,而现有治疗方式效果欠佳。因此,亟需寻找一种新的皮肤创面及纤维化治疗策略。腺苷在创面愈合和组织修复过程中起着重要作用,腺苷可通过激活其受体抑制炎症反应、促进血管生成、促进胶原合成,加速创面愈合,但腺苷受体的过度激活也可刺激成纤维细胞及胶原的异常增殖介导皮肤纤维化形成。该文就腺苷及其受体在皮肤创面愈合及纤维化中的作用作一综述,有望为再生医学的治疗策略提供一定思路及应用价值。     

低浓度过氧化氢对HaCat细胞增殖和大鼠创面愈合的作用与机制研究

目的 探讨低浓度过氧化氢(H2O2)对创面愈合的促进作用及其可能的作用机制.方法 建立大鼠全层皮肤缺损创面模型,将大鼠分为对照组(使用生理盐水)、高、低浓度H2O2组(分别使用3％、0.01％H2O2干预).选取第0、3、6、9、12、15、18天共7个时间点评估创面愈合率,并在第3、6、9天对创面组织样本进行组织病理...     

Osteopontin调控骨髓间充质干细胞(MSCs)对促进糖尿病足创面愈合的作用

目的:拟以C57糖尿病小鼠为研究对象,建立糖尿病小鼠OPN-/-MSCs组、糖尿病小鼠MSCs组及溶剂组对照组,采用小鼠创面愈合率检测、HE染色、免疫组化等试验方法,观察骨髓间充质干细胞(MSCs)及OPN基因敲除的MSCs对糖尿病小鼠创面愈合的影响.方法:原代提取MSCs及OPN-/-MSCs细胞;利用流式细胞仪检测细胞表面抗原;利用STZ溶液腹腔注射的方法建立糖尿病小鼠模型;将MSCs及OPN-/-MSCs分别注射至小鼠尾静脉,并观察创面愈合情况.结果:成功提取和培养了两组细胞,并成功建立了糖尿病小鼠模型;溶剂组小鼠完全愈合用了19.90± 0.55天,OPN-/-MSCs注射组完全愈合用了18.52±0.75天,MSCs尾静脉注射糖尿病组小鼠用了13.70±0.35天.尾静脉注射MSCs组创面愈合时间明显短于普通糖尿病小鼠组.结论:通过观察三组糖尿病小鼠创面愈合情况,证实MSCs尾静脉注射糖尿病组小鼠比OPN-/-MSCs注射组小鼠和溶剂组小鼠的创面愈合速度快,说明OPN具有调控骨髓间充质干细胞促进创面愈合的作用,为临床治疗糖尿病足提供新的理论依据.     

机械力调节细胞功能影响创面愈合的研究进展

创面愈合是指机体遭受外力作用,皮肤组织出现离断或缺损后愈合恢复的连续过程,包括各种组织再生、肉芽组织增生和瘢痕形成。创面愈合涉及多个细胞群、细胞外基质和各种信号分子,可以分为3个阶段：止血与炎症期、增殖期和重塑期。机械力作为细胞结构和功能的调节因素,参与调节创面愈合中多个细胞群的增殖、迁移和分化等生理过程,影响创面愈合的进程。现从细胞角度讨论机械力对创面愈合的影响。     

Chemical speciation in wound fluid leading to enhanced bioavailability for healing

ABSTRACT

ECCLES computer modelling is used to speciate Ca²⁺, Zn²⁺, Cu²⁺, Mn²⁺ and Fe³⁺ in wound fluid samples analysed for total metal content using Potentiometric stripping analysis. Bioavailability of metals, related to lipid soluble net-neutral complexes, was assessed and found to be broadly similar to the speciation in blood plasma. These appear to be benefits worthy of clinical investigation of keeping the wound fluid at pH = 6.4 and of raising the total cysteine concentration levels in wound fluid.     

Actin aggregation and embryonic epidermal wound healing

Recent experiments on the response of embryonic epidermis to wounding have revealed a cable of filamentous actin at the wound edge, which may be responsible for healing (Martin and Lewis 1991, 1992). We investigate the important question of how the cable forms as a response to wounding. We modify the mechanical model of Murray and Oster (1984) to investigate the post-wounding equilibrium in the epidermal sheet. We analyse the model in both one-dimensional and radially symmetric two-dimensional geometries, to determine the parameter domain in which a solution exists. We show that in both geometries the model solutions reflect the phenomenon of the actin cable for parameter values close to one edge of this domain. We interpret these results in terms of the relative rates of intracellular reorganization of actin and myosin, and thus suggest a possible mechanism for the formation of the actin cable.     

Antimicrobial and wound healing activities of certain Sudanese medicinal plants

The emergence of drug-resistant organisms have been increasing globally; therefore, it is a burning need to find an alternative drug to get rid of the diseases caused by resistant strains. This study aims to evaluate the antimicrobial and wound healing activities of Loranthus acacia, Cassia obtusifolia and Cymbopogon proximus plants. All the plants were collected and extracted — by maceration method. Antimicrobial activities determined using standard ATCC strain for Gram-positive bacteria (Bacillus subtilis, Bacillus crew, Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus) and Gram-negative bacteria (Shigella sonnnei, Salmonella Typhimurium, Salmonella typhi, Klebsiella pnuemoniae, Escherichia coli and Pseudomonas aeruginosa) following agar well diffusion method. Plants extracts were prepared as gel and investigated for in vivo wound healing activities in rats. Histological studies were performed on animals’ skin. The results showed that all tested plants have various antimicrobial and wound healing activities. Out of these plants, L. acacia exhibited the best result; it revealed a significant result for antimicrobial activities counter to all Gram-positive, Gram-negative bacteria and wound healing activities in comparing with the reference drug. Thus, it is essential to consider L. acacia as a prospective source in progress in the synthesis of a new antimicrobial drug for the treatment of infectious diseases.     

Cellular and molecular facets of keratinocyte reepithelization during wound healing

Cutaneous wound healing is a highly coordinated physiological process that rapidly and efficiently restores skin integrity. Reepithelization is a crucial step during wound healing, which involves migration and proliferation of keratinocytes to cover the denuded dermal surface. Recent advances in wound biology clarified the molecular pathways governing keratinocyte reepithelization at wound sites. These new findings point towards novel therapeutic targets and provide suitable methods to promote faster tissue regeneration in vivo.     

In vitro study of the impact of mechanical tension on the dermal fibroblast phenotype in the context of skin wound healing

Skin wound healing is finely regulated by both matrix synthesis and degradation which are governed by dermal fibroblast activity. Actually, fibroblasts synthesize numerous extracellular matrix proteins (i.e., collagens), remodeling enzymes and their inhibitors. Moreover, they differentiate into myofibroblasts and are able to develop endogenous forces at the wound site. Such forces are crucial during skin wound healing and have been widely investigated. However, few studies have focused on the effect of exogenous mechanical tension on the dermal fibroblast phenotype, which is the objective of the present paper. To this end, an exogenous, defined, cyclic and uniaxial mechanical strain was applied to fibroblasts cultured as scratch-wounded monolayers. Results showed that fibroblasts? response was characterized by both an increase in procollagen type-I and TIMP-1 synthesis, and a decrease in MMP-1 synthesis. The monitoring of scratch-wounded monolayers did not show any decrease in kinetics of the filling up when mechanical tension was applied. Additional results obtained with proliferating fibroblasts and confluent monolayer indicated that mechanical tension-induced response of fibroblasts depends on their culture conditions. In conclusion, mechanical tension leads to the differentiation of dermal fibroblasts and may increase their wound-healing capacities. So, the exogenous uniaxial and cyclic mechanical tension reported in the present study may be considered in order to improve skin wound healing.     

Insulin-like growth factor-I in wound healing of rat skin

Endothelin-1 is involved in physiology and pathophysiology of the alimentary tract. The peptide modulates blood flow in the gastrointestinal microvasculature and regulates contractility of smooth muscles and, when present in excess, may be an important factor contributing to pathogenesis of various forms of mucosal injury and peristaltic disorders. Mechanisms that regulate endothelin concentration in the gastrointestinal tissues are unknown. Therefore, the aim of our study was to identify and characterize endothelin inactivating peptidases in the rat gastrointestinal mucosa and smooth muscle cells. We have found three high affinity and efficient endothelin-1 inactivating peptidases. The acidic (pH optimum 5.5), membrane-bound, thiorphan- (ED(50) 1.2+/-0.2 nM) and phosphoramidon (ED(50) 150+/-25 pM) sensitive, endothelin-1 inactivating peptidase (K(M) 0.12+/-0.03 microM) was present in the mucosal cells of duodenum and small intestine. The enzyme exhibited high molecular weight (>100 kDa) and characteristics similar to that of the rat and human kidney, acidic metalloendopeptidase that was recently described. Two forms of the unique, low molecular weight (100>MW>30 kDa), alkaline (pH optimum 8.5), specific (K(M) 0.5+/-0.2 microM), thiorphan- and phosphoramidon insensitive, 1,10 phenanthroline inhibitable (ED(50) 0.65+/-0.20 mM, mean+/-S.E.M.) endothelin-1 inactivating peptidase were present exclusively in the duodenal mucosal cells; soluble form in cytosol and membrane-bound form exhibiting an abundance ratio 5:1, respectively. Mucosa of the stomach and large intestine, and gastrointestinal smooth muscle cells do not contain the specific endothelin-1 inactivating peptidases. The enzymes may play a crucial role in regulation of endothelin concentration in the gastrointestinal tissues. Whether impairment of activity of the mucosal endothelin inactivating peptidases, resulting in the increase of concentration of endothelin peptides in gastrointestinal tissues, occurs in various pathological conditions is actually studied in our laboratory.     

Wound currents and wound healing in the newt,Notophthalmus viridescens

Summary Wounded amphibian skin heals initially by a migration of epithelial cells from the cut edge towards the center of the wound. The density of currents leaving wounds made in Notophthalmus viridescens skin was manipulated in order to determine whether electrical fields associated with these currents might have a significant role in promoting this cell migration during wound healing. Wounds were made with either a needle (200 m) or a biopsy punch (500 m). Currents leaving the wounds were measured with a vibrating probe, and the wounds fixed at various times after wounding. When the Na⁺-dependent currents were reduced by blocking Na⁺ channels with benzamil, wound healing, as revealed by scanning electron microscopy and by paraffin histology, was impaired. These results are consistent with the hypothesis that there is an electrical component to wound healing.     

Effect of taurine on wound healing

Summary Taurine which has antioxidant effects is also known to have effects on cell proliferation, inflammation and collagenogenesis. The aim of this study was to investigate the effect of taurine on incisional skin wounds.The mice incised on the dorsal area were divided into control and experimental groups. Saline was injected intraperitoneally to half of the animals in the control group and locally applied to the other half. Fifty mM taurine solution was given intraperitoneally to the first half of the experimental animals and locally to the second half of the experimental group.After four days of treatment, malondialdehyde (MDA) and histamine levels as well as the tensile strength of the wound tissue were measured. Structural alterations in epidermis and dermis were histologically evaluated.The locally administreated taurine significantly increased wound tensile strength by decreasing the MDA and histamine levels and prevented the degranulation of the mast cells. These observations suggest that taurine may be useful on wound healing.     

Mathematical analysis of a basic model for epidermal wound healing

The stimuli for the increase in epidermal mitosis during wound healing are not fully known. We construct a mathematical model which suggests that biochemical regulation of mitosis is fundamental to the process, and that a single chemical with a simple regulatory effect can account for the healing of circular epidermal wounds. The numerical results of the model compare well with experimental data. We investigate the model analytically by making biologically relevant approximations. We then obtain travelling wave solutions which provide information about the accuracy of these approximations and clarify the roles of the various model parameters.