重组人表皮生长因子对大鼠皮肤烧伤愈合的促进作用

目的:观察局部应用重组人表皮生长因子(recombined human epidermal growth factor,rhEGF)对大鼠皮肤深Ⅱ度烧伤有无促进作用.方法:建立约10%的大鼠烧伤面积,测定给不同剂量的rhEGF治疗后不同时间的烫伤创面愈合面积,创面组织病理组织学以及测定愈合时间来观察rhEGF对皮肤创伤的治疗作用.结果: rhEGF小、中、大剂量(每cm2创面200 IU,400 IU,800 IU)可以缩短大鼠皮肤深Ⅱ度烧伤愈合的时间,同一时间内烧伤愈合面积高于对照组,同时还可以增加表皮细胞和毛细血管的增生,三个剂量之间未见明显的量效反应.结论:局部应用rhEGF可以促进大鼠皮肤烧伤愈合.     

硫化氢对糖尿病大鼠皮肤溃疡创面愈合的影响

目的:探讨硫化氢对糖尿病大鼠皮肤溃疡创面愈合的影响。方法:将30只健康雄性SD大鼠,随机分为正常对照组(NDC组)、糖尿病对照组(UDC组)和硫化氢处理组(TDA组),每组10只。腹腔注射链脲佐菌素(65 mg/kg)柠檬酸缓冲液(p H 4.5)建立糖尿病大鼠模型。1周后,将正常大鼠及糖尿病大鼠背部剪开直径为20mm的圆形切口,正常组和糖尿病组大鼠的溃疡创面以空白基质处理,硫氢化处理组则用2%的硫氢化钠涂抹溃疡创面。分别在给药后第5、10、15、20天测定伤口愈合率。21 d后处死大鼠,分别收集血浆以及肉芽组织,检测血浆的凝血酶原时间(prothrombin time,PT)、凝血酶时间(thrombin time,TT)及纤维蛋白原(fibrinogen,FIB),白细胞和淋巴细胞计数,ELISA检测血清超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量,Western blot检测肉芽组织中血红素加氧酶1(HO-1)和肿瘤坏死因子α(TNF-α)的表达水平;肉芽组织进行HE染色,光镜观察组织形态的变化。结果:与糖尿病组比较,硫氢化钠处理明显加快大鼠伤口愈合(P0.01),提高了血清SOD活性(P0.01),同时降低了MDA水平(P0.01);血液学检测显示,硫氢化钠明显降低白细胞及淋巴细胞数量,延长PT及TT,降低FIB水平。病理切片观察显示,糖尿病对照组大鼠肉芽组织有炎症细胞浸润,胶原纤维排列疏松且不规则,而硫化氢组大鼠肉芽组织中胶原排列整齐,血管生成增多(P0.05)。此外,TDA组HO-1表达明显高于UDC组,而TNF-α的水平则显著低于UDC组。结论:硫化氢可促进糖尿病大鼠伤口愈合,其机制可能与其提高抗炎及抗氧化作用、改善微循环进而修复组织损伤有关。     

A new mouse model for wound healing in hemophilia A

Purpose: To establish a new mouse model for wound healing studies on hemophilia A. Methods: Total 54 male mice with different genotypes including wild-type nude mice, heterozygous mice (FVIII^-/-/Nu) and FVIII deficient mice (FVIII^-/-) were generated and verified by PCR. Mice were subjected to wound healing research by making a 5 mm-thickness wound on mice skin and applying recombinant human epidermal growth factor (EGF, 10 μg/g) ointment, FVIII ointment (30 IU) or the ointment base to heal the wounds. Furthermore, keratinocytes were isolated from these newborn mice and subjected to migration assay by stimulation of EGF (ng/ml), insulin (10 μM) or vehicle. Results: A new hemophilic mouse model (FVIII^-/-/Nu) was constructed successfully after genotyping verified by PCR. Compared to FVIII^-/- mice, FVIII^-/-/Nu and Nu mice showed greater degree of wound contraction and loss of the crust. Topical treatment with EGF exhibited faster wound healing than FVIII and ointment base. Insulin treatment showed more increased migration distance than treated with EGF or vehicle. FVIII^-/-/Nu mice showed greater migration than FVIII^-/- and Nu mice. Conclusions: A new mouse model (FVIII^-/-/Nu) for wound healing in hemophilia A was constructed, and topical treatment of insulin may be a better therapy than EGF for healing wounds in hemophilia A.     

The mechanisms underlying fibroblast apoptosis regulated by growth factors during wound healing

While investigating the mechanisms underlying cell death during wound healing processes, we uncovered the pro‐apoptotic effects of basic fibroblast growth factor (bFGF) on granulation tissue fibroblasts following pretreatment with transforming growth factor (TGF)‐β1 in vitro. bFGF induced caspse‐3 activation and apoptosis in TGF‐β1‐pretreated granulation tissue‐derived fibroblasts (GF‐1) following bFGF treatment for 48 and 96 h. In contrast, fibroblasts that had been treated in the same manner and that originated from the uninjured dermis did not display apoptosis, indicating that the mechanisms underlying apoptosis events in fibroblasts that originate from normal dermal and wound tissues differ. In this process, we also found that bFGF inhibited Akt phosphorylation at serine 473 and induced a rapid loss of phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 in pretreated GF‐1 cells, an event that coincided with the dissociation of phosphorylated FAK from the focal adhesions. Therefore, inhibition of survival signals relayed via the disrupted focal adhesion structures and inactivated Akt following bFGF treatment may lead to apoptosis in GF‐1 cells pretreated with TGF‐β1. Pretreatment of GF‐1 with TGF‐β1 followed by the addition of bFGF resulted in significantly greater inhibition of phosphorylation of Akt and FAK compared to treatment with TGF‐β1 or bFGF alone. The combinatorial treatment also led to proteolysis of FAK and inhibition of FAK and Akt protein expression in GF‐1 cells. These findings demonstrated a significant role for the two cytokines in apoptosis of granulation tissue fibroblasts during wound healing. In vivo studies also confirmed a marked decline in phosphorylation and protein expression of Akt and FAK in bFGF‐injected skin wounds. These results led to the hypothesis that temporal activation of TGF‐β1 and bFGF at the injury site promotes apoptosis in granulation tissue fibroblasts, an event that is critical for the termination of proliferative granulation tissue formation. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

马桑提取物促进大鼠烧伤创面愈合的作用和机制

 目的：探讨马桑提取物(CSME)对大鼠烧伤创面愈合的影响及机制。方法：随机将40只SD雄性大鼠分成生理盐水（NS）组、白凡士林（WPJ）组、磺胺嘧啶银（SSD）组和CSME组,每组10只。将大鼠麻醉后,制备背部深Ⅱ度皮肤烧伤创面。而后分别用NS敷料、WPJ敷料、SSD敷料和CSME敷料覆盖治疗21 d。在第1 d、3 d、7 d、14 d和21 d,观察动物的临床症状和创面状况（上皮化速率、结痂及被毛等）后,分别取出创面组织,用于组织学观察,检测丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性,检测表皮生长因子（EGF）和碱性成纤维细胞因子（bFGF）蛋白水平及胶原mRNA表达。结果：CSME组新生上皮生长高度活跃,有大量新生被毛生长,创面上皮化速率明显高于其它各组 (P<0.05)。SSD组创面中央新生被毛稀疏而细小,而CSME组创面中央被毛密集,大部分被毛接近正常。CSME组镜下可见全部被多层上皮细胞覆盖,新生胶原纤维充分分化,排列整齐,组织结构明朗,皮脂腺和毛囊增生极其活跃等,显著优于其它各组。本研究显示,烧伤后从第1 d到21 d,CSME组早期EGF和bFGF水平显著高于其它各组,后期迅速下降,低于其它组（P<0.05或P<0.01）。SSD组Ⅰ型与Ⅲ型胶原mRNA表达的比值显著高于其它各组和正常组织,CSME治疗组显著低于其它各组和正常组织(P<0. 05)。结论：本研究表明,CSME可诱导烧伤创面无瘢痕愈合。CSME的这种作用与其早期增强EGF和bFGF蛋白水平,后期抑制两者的水平有关,也可能与其抑制烧伤创面Ⅰ型胶原而增强Ⅲ型胶原mRNA表达密切相关。     

A reliable method of determining wound healing rate

Several wound healing rate measures have been introduced with the main goal of enabling quantification of the effects of various therapeutic modalities on the healing of open wounds. Different definitions of wound healing rate render comparison of clinical results difficult. The goal of the present study was to propose a measure of wound healing rate that is independent of initial wound extent and to present a method of wound healing rate prediction. Comparisons were made of wound healing rate defined as absolute area healed per day, percentage of initial area healed per day and advance of the wound margin towards the wound centre per day. Analysis was performed on 300 wound cases. A disadvantage of wound healing measures that either use absolute area healed per day or percentage of initial area healed per day is their very limited use for comparing healing rates of wounds with different initial sizes. This disadvantage was overcome by incorporating a wound perimeter; thus obtaining a measure of the advance of the wound margin towards the wound centre. A definition of healing rate expressed as the greatest average wound margin distance from the wound centre divided by the time to complete wound closure is proposed. Because not all wounds are closed in the observation period, the time to complete wound closure has to be predicted. A method of wound healing rate prediction is presented based on a delayed exponential model the parameters of which are obtained from at least five weekly wound area measurements. Paired t-tests between actual time needed to complete wound closure and the predicted time resulted in p=0.062 after four, 0.484 after five and 0.900 after six weeks of observation.     

Effects of Zn-7® on open wound healing in dogs

Analysis of the accelerating effects of open wound healing by Zn-7 gel compared with normal saline was carried out in dogs. Five normal male, mixed breed dogs approximately 3 years old were selected. Histological and macroscopic aspects of second-intention wound healing were studied. Two rectangular, full-thickness skin wounds (20 × 30 mm) were created symmetrically on each dog at both sides of the dorsal midline at 0, 1, 2, 3, and 4 weeks. Left wounds were treated with Zn-7 gel (test group) and right wounds were treated with normal saline (control group) twice daily. Photographs were taken twice a week. Rulers were held vertically and horizontally close to the wound as a reference. The area of epithelialization and granulation tissue were measured for each wound, using the Scion Image software. Percentage wound contraction, epithelialization, and healing were calculated for each wound. No significant differences were observed in wound contraction, epithelialization and healing in the test and control groups (P > 0.05). At day 35 after initial wounding, biopsies were taken from wounds for histological examination. There were no significant differences in the number of inflammatory cells, fibrocyte, or amount of the fibrin and collagen (P > 0.05) between the test and control wounds.     

Oestrogens and wound healing

During the past few decades several studies have documented the deleterious impact of the menopause on bone mass and cardiovascular disease, and the reduction of risk in this area by HRT. However, the possible effects of the postmenopausal deficiency in ovarian hormones on skin and its repair post-injury, are less well documented. This review provides a survey of the literature that is available regarding the involvement and influence of oestrogens on the various phases of cutaneous repair — inflammation, proliferation and remodelling. Research carried out on the effects of oestrogens, both in terms of deficiency and replacement, on the process of wound healing in various animal models is described and discussed, together with the very limited work undertaken in humans. This area of research is of paramount clinical importance both in terms of financial cost and human suffering, since many chronic wounds such as venous ulcers, pressure sores and burns afflict the elderly population, of whom postmenopausal women comprise the majority. Clinically our aim should be to restore the integrity and function of wounded tissue as rapidly as possible after injury and it is generally believed that a better understanding of the effects of oestrogens on wound healing could lead to improved care of cutaneous wounds, and the treatment of not only the wound but of the postmenopausal woman as a whole.     

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。     

碱性成纤维细胞生长因子促进大鼠硬腭穿孔的愈合

目的:研究碱性成纤维细胞生长因子 (bFGF)对硬腭穿孔愈合的影响。方法:在大鼠硬腭部制作早期硬腭穿孔动物模型,外用bFGF治疗硬腭穿孔。采用肉眼观察、病理学检查的方法进行评价。结果:肉眼观察发现bFGF组伤口愈合率明显高于对照组(P＜0.01); 病理学检查表明bFGF能刺激肉芽组织的增长,成纤维细胞分裂增殖; bFGF组成纤维细胞的核仁形成区嗜银蛋白颗粒数目为3.73±0.52,对照组为2.11±0.31(P＜0.05)。结论: bFGF有助于肉芽组织的生长,具有显著促进硬腭穿孔创伤愈合的作用,有助于硬腭穿孔的修复。     

Heterogeneity of macrophage populations and expression of galectin-3 in cutaneous wound healing in rats

The aim of this study was to investigate the properties of macrophages that infiltrated the sites of cutaneous wound healing in rats between 1 and 26 days post wounding (dpw). During the inflammation phase (1–3 dpw), ED1⁺ (CD68⁺) macrophages with enhanced lysosomal activity dominated. From 5 to 7 dpw there was formation of granulation tissue as indicated by the presence of myofibroblasts expressing α-smooth muscle actin. At this stage, ED2⁺ (CD163⁺) macrophages, capable of producing inflammatory factors, were dominant. The majority of ED1⁺ macrophages expressed galectin-3, a regulator of fibrosis. Corresponding to the increased numbers of ED1⁺ and ED2⁺ macrophages at 3–9 dpw, there was increased expression of genes encoding transforming growth factor-β1 (a major fibrogenic factor), monocyte chemoattractant protein-1 and colony stimulating factor-1. These macrophage-related factors might contribute to inflammation and formation of granulation tissue. OX6⁺ macrophages expressing class II molecules of the major histocompatibility complex became predominant in the healing stages (15–26 dpw), indicating important roles for antigen-presenting cells in tissue remodelling. The OX6⁺ macrophages were most likely derived from ED1⁺ macrophages. The results of this study show that infiltration of phenotypically- and functionally-distinct macrophage populations characterizes different stages of the wound healing process.     

毛发生长周期对小鼠皮肤创伤愈合的影响

目的　探讨处于不同毛发生长周期的C57BL/6小鼠皮肤创伤愈合速度。 方法　制备小鼠皮肤创伤模型,计算术后0、3、7 d创面愈合率,愈合率=（原始创面面积－未愈合的创面面积）/原始创面面积×100%,比较毛发静止期（Hair telogen stages）小鼠和毛发生长期（Hair anagen stages）小鼠伤口愈合速度。采用HE染色比较伤口愈合的组织形态结构差异,利用BrdU检测伤口周围细胞增殖。 结果　毛发生长期的小鼠皮肤伤口愈合率显著高于毛发静止期的小鼠伤口愈合率。HE染色显示毛发生长期小鼠伤口周围表皮细胞层较多,且表皮细胞向伤口迁移增强;BrdU检测显示毛发生长期小鼠皮肤伤口周围表皮BrdU+ 细胞数多于毛发静止期小鼠。 结论　毛发生长期的小鼠皮肤创伤愈合率高于毛发静止期小鼠,这一结果为进一步探讨毛囊在创伤愈合过程中的作用提供研究基础,也为选择皮肤创伤愈合动物模型提供指导。     

MMP-9/TIMP-1表达在糖尿病鼠皮肤伤口愈合过程中的变化及意义初探

目的：观察基质金属蛋白酶-9（MMP-9）、组织金属蛋白酶抑制剂-1（TIMP-1）的表达和MMP-9/TIMP-1比值在糖尿病组和正常组大鼠皮肤伤口愈合过程中不同时点表达的动态变化，探讨其可能的作用机制。 方法:糖尿病大鼠形成6周后行皮肤伤口造模，采用HE染色、Masson染色和免疫组织化学方法评估伤口形成后3、7、14 d伤口组织的再上皮化、炎症细胞浸润、肉芽组织厚度、新生血管形成和胶原纤维密度的情况；通过逆转录-聚合酶链反应(RT-PCR)和Western印迹检测术后不同时点MMP-9、TIMP-1在伤口组织中的表达情况。结果:糖尿病大鼠伤口愈合明显迟缓。术后第3 d两组间胶原纤维、肉芽组织、新生血管和再上皮化没有差异，术后第7 d糖尿病组以上指标得分均低于正常组，第14 d这种趋势更加明显；而第3 d至14 d，糖尿病组的单核巨噬细胞浸润得分均低于正常组。术后第3 d两组MMP-9表达均达高峰，第7、14 d呈逐渐下降趋势，糖尿病组MMP-9表达水平在各时点均高于正常组；术后第3 d两组TIMP-1表达均达高峰，第7、14 d呈逐渐下降趋势，糖尿病组TIMP-1表达水平在各时点均低于正常组；正常组MMP-9/TIMP-1蛋白水平比值始终维持在一个动态平衡的稳定水平，而糖尿病组却长期处于高水平状态。结论:异常的胶原产生、新生血管重建、炎症反应、再上皮化、肉芽形成可能是糖尿病鼠创面愈合减慢的组织病理学基础；皮肤组织MMP-9/TIMP-1的平衡性改变可能是这种组织病理学异常的重要原因之一。     

外源性透明质酸对创面愈合影响的研究进展

对透明质酸参与创面修复过程及其机制的研究进展进行综述,回顾、总结与分析透明质酸盐的理化性质、代谢途径及代谢产物与创面修复的关系。透明质酸盐在创面修复过程中具有清创、抗炎、促进创伤愈合重要作用,其代谢产物能够促进血管生成及成纤维细胞增殖,调控胶原合成。透明质酸盐凭借在创面修复的重要作用,将会在创面修复及组织工程等领域得到广泛的应用。     

皮肤成纤维细胞在创面愈合中的研究进展

皮肤成纤维细胞是参与创面愈合的主要修复细胞,近年来其异质性及其与周围细胞间的通讯正逐渐引起重视.真皮成纤维细胞亚群主要包括乳头状成纤维细胞和网状成纤维细胞,对创面愈合发挥不同的作用.成纤维细胞通过自分泌和旁分泌信号分子与周围细胞之间相互作用构成创面微环境,影响创面愈合.慢性创面中的成纤维细胞表现出多种功能障碍.本文就成...     

大鼠皮肤创伤修复过程中转化生长因子β1和β3的表达

背景：转化生长因子β在组织创伤修复中发挥核心和关键作用。 目的：观察转化生长因子β1和转化生长因子β3在大鼠皮肤瘢痕性创伤愈合过程中表达量及表达部位的变化。 方法：制备大鼠皮肤全层切伤模型,长度1.5-2.0 cm,深及筋膜层。于伤后0 h,12 h,1 d,2 d,3 d,4 d,5 d,6 d,7 d处死大鼠,取损伤部位皮肤,采用免疫组织化学染色检测各时间点转化生长因子β1和转化生长因子β3的表达,并进行定量分析。 结果与结论：免疫组织化学染色显示,在创伤愈合的早期阶段(伤后1-5 d),转化生长因子β1和转化生长因子β3免疫阳性颗粒主要出现在上皮细胞、上皮基底层细胞胞浆、巨噬细胞等免疫细胞胞浆及肉芽组织中;随着创伤修复时间的持续,免疫阳性颗粒主要出现在真皮层的成纤维细胞及细胞外基质中。其中转化生长因子β1的表达在创伤后1-5 d最强,而转化生长因子β3在创伤后六七天时开始明显表达。可见在大鼠皮肤瘢痕性创伤愈合过程中,转化生长因子β1的表达先于转化生长因子β3,提示转化生长因子β1与胶原形成及创伤修复关系密切,而转化生长因子β3在愈合后期表达量有升高趋势,其可能与创伤后期的组织改建密切相关。     

诱导型一氧化氮合酶对骨骼肌损伤再生的影响

目的　观察骨骼肌损伤再生中的细胞形态学变化和损伤后诱导型一氧化氮合酶（inducible nitric oxide synthase, iNOS）的表达水平;观察巨噬细胞上清液对iNOS表达水平和骨骼肌再生的影响。 方法 制备SD大鼠骨骼肌损伤模型,损伤3 d后获取骨骼肌,进行HE染色、iNOS免疫组化分析;利用原代培养的巨噬细胞上清液处理小鼠C2C12成肌细胞株,RT-PCR技术探讨巨噬细胞和成肌细胞相互作用的分子机制。 结果 HE染色可见,骨骼肌损伤处有新的血管产生并进入损伤的骨骼肌内;损伤部位iNOS表达强阳性,生发区iNOS表达呈阳性,正常与损伤细胞表达差异明显;巨噬细胞上清液处理小鼠C2C12成肌细胞株能够促进iNOS和成肌细胞因子MyoD的表达。 结论 骨骼肌损伤过程中,iNOS的表达增加能够促进骨骼肌的再生,加快骨骼肌的损伤修复。     

Modelling of chronic wound healing dynamics

Following chronic wound area over time can give a general overview of wound healing dynamics. Decrease or increase in wound area over time has been modelled using either exponential or linear models, which are two-parameter mathematical models. In many cases of chronic wound healing, a delay of healing process was noticed. Such dynamics cannot be described solely with two parameters. The reported study deals with two-, three-, and four-parameter models. Assessment of the models was based on weekly measurements of 226 chronic wounds of various aetiologies. Several quantitative fitting criteria, i.e. goodness of fit, handling missing data and prediction capability, and qualitative criteria, i.e. number of parameters and their biophysical meaning were considered. The median of goodness of fit of three- and four-parameter models was between 0.937 and 0.958, and the median of two-parameter moels was 0.821 to 0.883. Two-parameter models fitted wound area over time significantly (p=0.001) worse than three- and four-parameter models. The criterion handling missing data provided similar results, with no significant difference between three- and four-parameter models. Median prediction error of two-parameter models was between 111 and 746; three-parameter models resulted in an error of 64 to 128, and finally four-parameter models resulted in the highest prediction error of 407 and 238. Based on the values of quantitative fitting criteria obtained, three parameters were chosen as the most appropriate. Based on qualitative criteria, the delayed exponential model was selected as the most general three-parameter model. It was found to have good prediction capability and in this capacity it could be used to help physicians choose the most appropriate treatment for patients with chronic wounds after an initial three-week observation period, when the median error increase of fitting is 74%.     

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。     

Allotransplantation of ascorbic acid-treated fibroblasts improves healing of excisional cutaneous wound in diabetic rats

The purpose of this study was to evaluate the effects of ascorbic acid (AA)-treated fibroblasts transplantation on excisional diabetic wound healing. An excisional wound was created between the shoulders of streptozotocin-induced diabetic rats. On day three, 1 ml of PBS, ?1 × 10⁶ ?intact homologous fibroblasts, and ?1 × 10⁶ ? fibroblasts treated with 50 μM AA were injected subcutaneously around the wound edges in control, treatment-1 and treatment-2 groups, respectively. In the sham group, the wound was left intact. Wound area was measured by planimetry. On day 15, samples were harvested for histopathological examination and hydroxyproline content. Wound area in treatment-1 and ? 2 groups was ?significantly decreased compared to other groups, on days 11 and 15. The hydroxyproline content was significantly lower in the control group compared to the other groups. Histopathology revealed significant increases in the number of neovessels, macrophages, lymphocytes and fibroblasts in the treatment-2 group compared to the other groups. Trichrome staining showed the highest level of collagen deposition and orientation in the treatment-2 group. In conclusion, allotransplantation of ?50 μM ? AA-treated fibroblasts ?could result in progressive healing and improved reparative indices of excisional dermal wound in diabetic rats.