凝血酶肽促进缺血创面愈合与皮瓣存活的实验研究

目的探讨凝血酶受体激活肽(TP508)对促进缺血创面愈合与皮瓣存活的作用.方法SD大鼠66只,制作部分缺血创面(16只)、完全缺血创面(16只)、正常创面(18只)及皮瓣(16只)模型,每一模型又分为TP508治疗组和等渗盐水对照组.术后第3、7、10、14天,将创面或皮瓣坏死轮廓描记至醋酸纸七,输入计算机求出创面面积或坏死面积.结果术后7 d和14 d,TP508组正常创面面积仅为对照组的73.7%和45.4%.术后7 d,TP508组部分缺血创面面积为(99.8±30.7)mm2,而对照组为(128.0±43.4)mm2.术后第10天,TP508组完全缺血创面面积为(293.0±34.0)mm2,对照组为(352.4±41.2)mm2.术后第7天,TP508组皮瓣坏死面积为对照组皮瓣坏死面积的80.4%,第14天为56.8%.结论 TP508对促进大鼠缺血创面愈合和皮瓣存活均有显著作用.     

转Endostatin基因角朊细胞移植对烧伤深Ⅱ°创面愈合及瘢痕增生的影响

目的探讨转内皮生长抑制素(ES)基因角朊细胞移植对烧伤深Ⅱ°创面愈合及瘢痕增生的影响。方法将人体皮肤移植于裸鼠并造成深Ⅱ°烧伤创面。实验分为对照组(11只)、单纯角朊细胞移植组及转ES基因角朊细胞移植组(各10只)。对照组不行细胞移植,创面自行愈合;单纯角朊细胞移植组创面移植培养人角朊细胞;转基因移植组移植转ES基因角朊细胞。观察各组裸鼠创面愈合特点、瘢痕增生情况,并对愈合区组织进行病理切片检查、检测愈合区皮肤组织ES 蛋白表达、I、Ⅲ型前胶原含量。结果转基因移植组裸鼠创面愈合时间(13±5)d与单纯移植组 (14±5)d差异无统计学意义(P>0．05),但明显短于对照组[(25±7)d,P<0．01]。对照组裸鼠创面愈合后瘢痕增生明显,伤后100 d厚度≥0．22 cm,单纯移植组瘢痕增生厚度≥0．17 cm,转基因移植组仅有轻度瘢痕增生,愈合区皮肤组织ES蛋白检测阳性。单纯移植组、转基因移植组愈合区组织前胶原I含量(65．3±8．5)μg／g,(61．4±7．0)μg／g、前胶原I／前胶原Ⅲ比例(0．66±0．15,0．57± 0．13)明显低于对照组(1．51±0．37,P<0．01),而前胶原Ⅲ含量显著高于对照组(P<0．01)。结论转ES基因移植既可加速创面封闭,又能抑制愈合后瘢痕形成。     

表皮细胞膜片与猪去细胞真皮基质复合的移植

目的观察鼠表皮细胞膜片与猪去细胞真皮基质复合移植修复全层皮肤缺损的可行性和效果。方法以SD乳鼠的第3代表皮细胞制备细胞膜片,高渗盐水/氢氧化钠法制备猪去细胞真皮基质。36只SD大鼠全层皮肤缺损创面,分别行去细胞真皮基质与表皮细胞膜片复合移植和单纯表皮细胞膜片移植。结果两组创面术后均未见对移植物的急性期免疫排斥反应,第2、4、6周复合植皮组移植物成活率分别为(77.05±4.69)%、(83.12±5.13)%、(90.66±4.87)%,与细胞膜片移植组差异无统计学意义(P>0.05),但移植物收缩率显著减低,分别为(9.84±2.33)%、(18.97±3.40)%、(25.92±3.11)%(P<0.05)。复合植皮组上皮化良好,胶原纤维排列有序,基底膜结构完整。结论复合移植适用于修复全层皮肤缺损,能改善创面愈合质量。     

重组人表皮生长因子促进大鼠皮肤创面愈合的研究

目的观察重组人表皮生长因子(rhEGF)对皮肤创面愈合的作用。方法制作大鼠背部创伤模型,采用自身平行对照,将34只大鼠背部的68个创面分成rhEGF治疗组与盐水对照组,观察大体形态和组织学改变、创面愈合时间和愈合率,测定伤后不同时间创面羟脯氨酸(OHP)含量和Ⅰ型Ⅲ型胶原比例,进行细胞DNA周期分析。结果经rhEGF治疗的创面愈合速度较盐水对照明显加快,2组平均愈合时间为(17.2±1.3)d和(20.5±1.6)d(P<0.01);外用rhEGF使创面肉芽组织生成增多,再上皮化明显,显著增加创面中OHP含量,降低Ⅰ型Ⅲ型胶原比例,加速细胞DNA复制。结论外用rhEGF可缩短创面愈合时间,增加肉芽组织及OHP含量,降低Ⅰ型Ⅲ型胶原比例,加速细胞DNA复制,明显促进皮肤创面的修复。     

重组人角质细胞生长因子2涂膜剂对家兔损伤创面愈合的影响

目的观察重组人角质细胞生长因子2(rhKGF-2)涂膜剂对家兔损伤创面愈合的影响。方法用预热至100℃的100 g砝码在家兔背部脱毛部位压烫8 s,造成背部4个直径为2．5 cm 的深Ⅱ度烫伤创面;手术切除家兔背部部分皮肤,制作2个5．5 cm×4．0 cm的全层皮肤缺损创面。伤后第2天将家兔分成对照组、基质组、rhKGF-2溶液组和不同剂量rhKGF-2涂膜剂组,共12个组 (两种创面各6组),每天分别在创面涂抹等渗盐水、涂膜剂基质、rhKGF-2溶液及3种剂量的rhKGF-2 涂膜剂,连续给药15 d。每4天测量1次伤口面积并计算愈合率,第16天切取各组家兔伤口及其周围正常皮肤进行组织形态学观察,利用Masson三色法染色和MOTIC Advanced 3．2形态分析软件统计创面新生上皮面积、厚度和上皮细胞迁移距离。结果 30．0 μg rhKGF-2涂膜剂给药4、12 d时, 家兔的烫伤创面愈合率[(20±4)％、(65±6)％]明显高于对照组[(10±4)％、(56±9)％]和基质组 [(20±5)％、(59±7)％];160．0 μg rhKGF-2涂膜剂给药4、12 d时,家兔的皮肤缺损创面愈合率 [(33±6)％、(71±20)％]明显高于对照组[(23±4)％、(53±6)％]和基质组[(27±11)％、(58± 9)％]。组织形态学定量检测结果显示,rhKGF-2涂膜剂尤其是大剂量组能明显增加两种创面新生上皮面积、平均厚度和上皮细胞移行距离。结论 rhKGF-2涂膜剂能明显加快家兔皮肤烫伤和皮肤全层切除创面周围上皮细胞的增生与迁移,缩短其愈合过程。     

自体表皮细胞-纤维蛋白膜创面移植治疗大鼠烧伤

目的：观察自体表皮细胞-纤维蛋白膜移植到大鼠烧伤创面治疗皮肤缺损的效果。方法：健康Wistar大鼠20只,随机分成烧伤皮肤缺损造模组和自体表皮细胞-纤维蛋白膜移植治疗组,治疗后计算表皮细胞在纤维蛋白膜上最佳接种密度,观察移植后的各组创面愈合情况、创面伤口的收缩比例等。结果：在纤维蛋白膜上接种表皮细胞的最佳密度为5×10^4／cm2,烧伤皮肤缺损造模组创面完全愈合时间平均22．3d,自体表皮细胞-纤维蛋白膜移植治疗组为18．1d,造模组创面收缩率为（70±5）％,移植组为（20±5）％（均P〈0．05）。结论：自体表皮细胞-纤维蛋白膜可用于覆盖大面积烧伤造成的皮肤缺损,预防创面伤口瘢痕化的形成,减轻创面收缩率,加速皮肤缺损创面的愈合速度。     

嵌合体大鼠诱导异种皮肤移植免疫耐受的初步研究

目的 探讨嵌合体大鼠诱导异种皮肤移植免疫耐受的可行性。方法 采集兔骨髓干细胞，经行宫内胎鼠移植以及对新生子鼠行肝内注射，制作兔骨髓干细胞嵌合体大鼠模型。6周后将15只嵌合体大鼠分为A组（8只）、B组（7只）。将A组大鼠皮肤移植给供髓兔，将7只非嵌合体大鼠皮肤移植给非供髓兔作A组对照；将B组大鼠、7只非嵌合体大鼠（B组对照）皮肤同时移植给供髓兔。记录移植后皮片成活时间、创面愈合时间。结果A组对照移植皮片成活（9．3±1．8）d，创面于（20．9±2．1）d愈合；A组移植皮片成活（15．1±2．6）d，创面于（18．5±1．3）d愈合。B组及其对照移植皮片的成活时间、创面愈合时间与A组相似。与各自对照皮肤移植相比，A、B组皮片成活时间延长（P〈0．01），创面愈合时间缩短（P〈0．05或P〈0．01）。结论 嵌合体大鼠行异种皮肤移植后能诱导移植皮片免疫耐受．使其成活时间明显延长．创面愈合时间缩短。     

失神经支配大鼠皮肤切割创面愈合过程中修复细胞增生活性的研究

目的:研究大鼠失神经支配皮肤切割伤愈合过程中修复细胞增生活性的变化。方法:40只SD大鼠随机分成T、C两组(每组20只),在其背部形成全层皮肤切割伤缺损创面,其中T组为手术损伤鼠T11～L12脊神经皮肤切割伤组,C组为正常有神经支配的皮肤切割伤组,在伤后1、2、3、4周,观察创面愈合,A、B两组同时取材,采用免疫组化和银染法,检测创面修复细胞PCNA的表达和AgNORs颗粒数的变化。结果:T组较C组创面愈合明显延迟,同时修复细胞PCNA表达明显减弱,细胞核内AgNORs颗粒数明显减少,第3周两组的创面PCNA标记指数和AgNORs计数分别为2.11%/18.1%(P=0.001),1.1/3.1个/细胞(P<0.05)。结论:大鼠失神经支配皮肤切割伤愈合较正常创面愈合明显延迟,修复细胞增殖活性明显降低。     

深Ⅱ度烫伤大鼠创缘皮肤组织中表皮细胞增殖的研究

目的观察大鼠深Ⅱ度烫伤后创缘皮肤组织中表皮细胞的增殖活动规律,探讨其可能机制. 方法将24只SD大鼠随机分为正常组(未烫伤)、烫伤后3 d组、7 d组及14 d组,每组6只.采集正常组大鼠皮肤及烫伤大鼠创缘皮肤,观察其表皮组织学特征;用流式细胞仪检测表皮细胞的细胞周期;蛋白印迹法检测表皮细胞增殖调节因子细胞周期素(cyclinD1、cyclinB1)和细胞周期素依赖性激酶(CDK)4的表达水平,并测定M期促进因子(MPF)的组蛋白激酶活性. 结果组织学观察显示,伤后3 d组大鼠创缘表皮细胞核及核仁较正常组增大;伤后14 d组胞核及核仁增大明显,细胞数显著增多.伤后14 d组S期表皮细胞百分比出现上升趋势;G2/M期百分比自伤后3 d起逐渐升高,伤后7、14 d组(4.5±0.6、5.4±1.0)显著高于正常组(2.9±1.1,P<0.05).cyclinD1表达量伤后3 d即明显增高;cyclinB1表达无显著波动.伤后3 d组的CDK4表达水平较低,14 d组开始回升.伤后14 d组表皮细胞MPF活性显著增强. 结论在细胞周期调控因子作用下,大鼠深Ⅱ度烫伤后皮肤组织中表皮细胞在伤后早期即出现DNA合成及有丝分裂的增加,伤后14 d增殖明显活跃.cyclinD1/CDK4复合物的表达及MPF的活性在伤后早期并未同步增高,但自伤后14 d起其表达显著增多,提示创面愈合过程中细胞周期调控因子的调控规律具有特殊性.     

自体表皮细胞悬液移植修复全层皮肤缺损创面的动物实验研究

目的探讨自体表皮细胞悬液移植技术用于全层皮肤缺损创面修复的适宜密度。方法取健康清洁级成年SD大鼠40只,雌雄不限,体质量210~230 g;根据细胞移植密度不同,随机分为高、中、低细胞密度及空白组(分别为A、B、C、D组,n=10)。取大鼠背部皮肤培养表皮细胞,并制作大鼠全层皮肤缺损创面抗挛缩模型。其中A、B、C组分别将0.2 mL密度为1×10~6、1×10~5、1×10~4个/cm~2的自体表皮细胞悬液移植至创面处,D组给予等量限制性角质形成细胞无血清培养基;取成年Wistar大鼠背部皮肤制备同种异体皮,覆盖各组创面。术后观察大鼠存活情况,于术后7、14、21 d大体观察同种异体皮成活、脱落及创面愈合情况,同种异体皮脱落后计算创面愈合率;21 d时取材行组织学及免疫组织化学染色,观察创面修复情况。结果术后大鼠均存活至实验完成。各组大鼠同种异体皮随时间延长逐渐成活,干燥并开始脱痂;至21 d同种异体皮基本脱落后A、B组创面可见成片上皮,C组创面可见少量菲薄上皮,D组创面无上皮形成。术后21 d同种异体皮脱落后,A、B、C、D组创面愈合率分别为62.9%±9.6%、64.2%±9.1%、38.5%±5.7%、22.7%±5.5%,A、B组创面愈合率显著高于C、D组(P0.05),C组高于D组(P0.05),A、B组间比较差异无统计学意义(P0.05)。组织学观察示,A、B、C组愈合的创面上皮层可见鳞状上皮细胞,A、B组表皮分层明显,C组表皮层薄、可见炎性细胞浸润,D组为肉芽组织。免疫组织化学染色观察示,A、B、C组表皮-真皮连接层Ⅳ型胶原和Ⅶ型胶原表达呈阳性,D组无表皮层呈阴性;A、B组Ⅳ、Ⅶ型胶原表达阳性细胞百分比显著高于C组(P0.05),A、B组间比较差异无统计学意义(P0.05)。结论自体表皮细胞悬液移植技术在大鼠全层皮肤缺损创面修复中可重构皮肤,1.0×10~5个/mL为创面修复的适宜移植密度。     

Thrombin peptide TP508 stimulates cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues

The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-three-amino-acid peptide that represents a portion of the receptor-binding domain of the native human thrombin molecule that has been identified as the binding site for a specific class of receptors on fibroblasts and other cells. Preclinical studies with this peptide have shown that it can accelerate tissue repair in both soft and hard tissues by mechanisms that appear to involve up-regulation of genes that initiate a cascade of healing events. These events include recruitment and activation of inflammatory cells, directed migration of cells (chemotaxis), cell proliferation, elaboration of extra-cellular matrix, and accelerated revascularization of the healing tissues. Early preclinical dermal wound-healing studies showed that TP508 accelerated healing of both incisional wounds and full-thickness excisional wounds in normal and ischemic skin. In all of these studies, the accelerated healing was associated with increased neovascularization across the incision or in the granulating wound bed. Studies in a rat fracture model have also shown that TP508 accelerates the rate of fracture repair. Gene array analysis of fracture callus from control and TP508-treated fractures indicated that TP508 treatment was associated with an up-regulation of early response elements, inflammatory mediators, and genes related to angiogenesis. Similar to what had been seen in dermal wounds, histology from rat fracture callus twenty-one days after treatment indicated that fractures treated with TP508 had significantly more large functional blood vessels than did fractures in the control animals. In vitro studies support these in vivo data and indicate that TP508 may have a direct angiogenic effect by promoting the rate of new vessel growth. The results from phase-1 and phase-2 human clinical studies have shown a positive stimulatory effect of TP508 in the healing of diabetic ulcers and in the repair of fractures to the distal aspect of the radius. Collectively, these studies suggest that TP508 accelerates tissue repair by initiating a cascade of events that lead to an increased rate of tissue revascularization and regeneration.     

粉防己碱对皮肤瘢痕组织细胞增殖和凋亡的影响

目的　探讨粉防己碱 (Tet)对皮肤创面愈合瘢痕组织细胞增殖周期和凋亡相关基因bcl 2表达的影响。方法　建立兔耳皮肤创面愈合模型 ,术后 2 8d ,将 2 0只新西兰白兔 68个瘢痕创面随机分组分别用Tet、去炎松及生理盐水行瘢痕内注射 ,应用苏木素 伊红 (HE)染色、胶原纤维(Von Gieson)染色分析和透射电子显微镜观察细胞增殖和胶原代谢变化 ;运用流式细胞光度分析检测创面愈合瘢痕组织细胞周期和bcl 2蛋白表达率。结果　组织病理学观察显示 ,Tet治疗组、去炎松阳性对照组瘢痕组织细胞数量和胶原密度均较生理盐水阴性对照组显著减少。流式细胞检测结果 ,Tet治疗组、去炎松阳性对照组与生理盐水阴性对照组比较 ,差异均有非常显著性 (P <0 .0 1) ;Tet治疗组与去炎松阳性对照组之间的差异无显著性 (P >0 .0 5 )。结论　Tet对兔耳创面愈合瘢痕组织细胞增殖具有明显抑制作用     

Thrombin peptide TP508 accelerates closure of dermal excisions in animal tissue with surgically induced ischemia.

TP508 is a synthetic peptide corresponding to amino acids 508 through 530 of human prothrombin. We previously demonstrated that a single topical application of TP508 stimulates revascularization and healing of acute incisional and excisional wounds in normal, healthy rat skin. To determine if TP508 would enhance wound healing in ischemic skin, we used bipedicle flaps, cranially based flaps, and free grafts to surgically create ischemic regions on the backs of rats. Full-thickness, circular excisions were made within the flaps or grafts and immediately treated with a single application of saline +/- TP508 (0.1 microg/wound). Compared to wound closure in normal skin, ischemic skin wounds exhibited delayed closure, and the length of delay correlated with the degree of surgically induced ischemia. TP508 significantly accelerated closure in both normal and ischemic skin, resulting in closure rates that were increased within the first 7 days of wounding by 30% in normal tissue and bipedicle flaps, 50% in cranially based flaps, and 225% in free grafts. Moreover, in both flap models, TP508 restored the rate of closure to a rate approximating the control rate observed in normal skin. Histological comparisons of wound tissue from normal skin and cranially based flaps showed that ischemia reduced early recruitment of inflammatory cells at day 1 but increased inflammatory cell numbers in wound beds at day 14. TP508 treatment of ischemic flap wounds significantly increased early inflammatory cell recruitment and restored the normal rapid resolution of the inflammatory phase. In addition, at day 7, TP508-treated wounds appeared to have an increased number of large functional blood vessels compared to saline controls. These studies support the potential efficacy of TP508 in treating ischemic wounds in humans.     

β-1 and β-2, but not α-1 and α-2, adrenoceptor blockade delays rat cutaneous wound healing

The sympathetic nervous system plays an important role in wound healing, but its mechanism of action is poorly understood. The aim of this study was to investigate the effects of β- and α-adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (β1- and β2-antagonist), atenolol (β1-antagonist), or phentolamine (α1- and α2-antagonist) dissolved in drinking water. A full-thickness excisional lesion was created and the wound area was measured. Fourteen days after wounding, lesions and adjacent skin were removed, formalin-fixed, and paraffin-embedded. Sections were stained with hematoxylin–eosin and toluidine blue, and immunostained for α-smooth muscle actin and proliferating cell nuclear antigen. Wound contraction was delayed in propranolol- and atenolol-treated animals but not in phentolamine-treated animals. Reepithelialization was decreased only in propranolol-treated animals. β1- and β2-adrenoceptor blockade delayed leukocyte migration, epidermal and connective tissue cell proliferation, myofibroblastic differentiation, and mast cell migration. The volume density of blood vessels was increased in the propranolol- and atenolol-treated animals compared with controls. The levels of matrix metalloproteases (MMP-2 and MMP-9) decreased in the propranolol- and atenolol-treated animals. α1- and α2-adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro-MMP-9 levels. In conclusion, β-1 and β-2, but not α-1 and α-2, adrenoceptor blockade delays cutaneous wound healing.     

Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508

Thrombin is an essential factor in hemostasis, inflammation, and tissue repair. The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors and mimics cellular effects of thrombin at sites of tissue injury. Treatment of full-thickness excisional wounds in normal rats with a single topical application of 0.1 microg TP508 (14 pmol/cm2) reproducibly accelerates wound closure, yielding wounds that on average close 39% more than controls by day 7 (p < 0.001). Wounds treated with 1.0 microg TP508 are 35% and 43% (p < 0.001) smaller than controls on day 7 and 10, respectively. The early rate of closure is approximately 40% greater in TP508-treated than vehicle-treated wounds (20 versus 14 mm2/day) and remains higher through day 7. Breaking strength after closure is slightly greater (15-23%) in wounds treated with TP508 than with saline alone. Histologic comparisons show that TP508 enhances recruitment of inflammatory cells to the wound site within 24 hours post-injury. TP508 treatment also augments revascularization of injured tissue, as evidenced at day 7 by the larger size of functional vessels in the granulation tissue and by the directed development of blood vessels to wounds. These studies raise the possibility that TP508 may be clinically useful in management of open wounds.     

Bioactive interleukin-8 is expressed in wounds and enhances wound healing

BACKGROUND: Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing. MATERIALS AND METHODS: Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model. RESULTS: IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8. CONCLUSIONS: These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.     

神经生长因子加速猪深Ⅱ度烧伤创面愈合的实验

目的 探讨神经生长因子(nerve growth factors，NGF)对猪烧伤创面愈合的影响。方法 小白家猪6只，用控温控压仪在其背部制成24个直径为2．5cm的深Ⅱ度创面，随机分为4组，每6个创面为1组，即等渗盐水对照组，NGF1、2．5、5μg／ml治疗组。治疗后3、5、9d进行组织学检查、羟脯氨酸测定、细胞DNA周期分析及各组创面愈合时间比较。结果 治疗组上皮增生活跃且上皮化较对照组提前；治疗组创面组织羟脯氨酸含量，均有一个先下降后升高的过程，尤其在第5天，与对照组相比明显下降；细胞DNA周期分析表明，治疗组在S期细胞数较对照组均有明显增多；创面愈合时间较对照组提前。结论 局部应用NGF能促进烧伤深Ⅱ度创面愈合。     

Involvement of RNA helicase p68 in skin wound healing process in rats

Purpose: RNA helicase p68 plays an important role in organ development and maturation through tuning cell proliferation. However, the character and role of p68 in the whole wound healing process need more study. Methods: First, we characterize expression of p68 in normal rat skin development postnatal. Then, we assayed dynamic change of p68 in rat skin from different stage after injury, and explored the role of p68 in proliferation and migration of three types of wound healing related cells. Results: p68 was down-regulated during skin developmental and maturation process, up-regulated after wound, peaked on day 14 and then significantly decreased. Wound fluid enhanced wound healing related cell proliferation and up-regulated expression of p68. Conversely, reducing p68 expression by RNA interference resulted in significantly slower proliferation and migration. Conclusion: Our results define an important role of RNA helicase p68 in skin wound healing process.     

Inhibition of wound repair by thymic hormones

To further define the role of the thymus in wound healing, we studied the effects of two thymic hormones on fibroplasia in normal euthymic and in nude athymic mice. Groups of 10 mice underwent a 2.5 cm dorsal skin incision with subcutaneous placement of polyvinyl alcohol sponges. Starting on the day of wounding, the following daily injections were given: (1) thymopentin (TP5), an active synthetic pentapeptide of thymopoietin, a naturally occurring thymic hormone (1 microgram/day/IM); (2) thymulin or facteur thymique serique (FTS), a naturally occurring circulating thymic hormone (0.2 microgram/day/IM); (3) control saline solution (0.1 ml/day/IM). All mice were killed 4 weeks after wounding, and wound breaking strength and hydroxyproline content of the sponge granulomas were measured. The results show that both thymic hormones impaired wound breaking strength and reparative collagen synthesis in normal and athymic mice. The magnitude of the wound healing impairment induced by the two hormones was equal in the thymus-bearing and in the nude mice. The data support previous findings, which suggested that the thymus has an inhibitory effect on wound healing.