原代培养过程中壳聚糖衍生物对CTCF/YB-1/C-myc和p53蛋白表达的影响

成功建立了人增生性瘢痕细胞和正常皮肤成纤维细胞的原代培养, 并利用热休克蛋白(HSP47)和成纤维细胞特异蛋白(FSP)标记物进行了鉴定。研究发现, 经过壳聚糖衍生物处理, 人增生性瘢痕成纤维细胞和正常皮肤成纤维细胞在培养中均出现了不同类型的蛋白表达。多功能转录因子蛋白(CTCF)在壳聚糖衍生物处理的增生性瘢痕成纤维细胞中出现表达上调; 在聚糖衍生物处理的正常皮肤成纤维细胞中数量无变化。YB-1结合蛋白在经壳聚糖处理的正常皮肤成纤维细胞与人增生性瘢痕细胞中的表达几乎无异, 但在未经壳聚糖处理的细胞中表达不同。C-MYC和P53蛋白在壳聚糖衍生物处理的增生性瘢痕纤维细胞中表达上调, 但在正常皮肤成纤维细胞中, 无论是否经过壳聚糖衍生物处理, 这两种蛋白都没有表达。上述4种蛋白在人增生性瘢痕细胞和正常皮肤成纤维细胞中表现出不同的表达方式, 这种新型壳聚糖衍生物可能在控制人增生性瘢痕细胞和正常皮肤成纤维细胞生长和增殖过程中起着重要作用。这些蛋白因子的表达机制目前还不是完全清楚, 有待于进一步研究。     

原位杂交检测microRNA-150在增生性瘢痕中的表达

瘢痕是人体在创伤修复过程中的必然产物,而增生性瘢痕是皮肤在创伤修复过程中成纤维细胞过度增生的表现。本研究的目的是探讨micro RNA-150在皮肤增生性瘢痕组织结构中的表达情况。本研究通过HE染色显示正常皮肤组织和增生性瘢痕的结构差异与病变的形态结构特点;利用Masson染色鉴别增生性瘢痕中胶原纤维和肌纤维的组织形态;进一步原位杂交检测皮肤增生性瘢痕micro RNA-150的表达。原位杂交分析显示,按着色细胞染色强度分为:高表达记为(+),未表达和低表达记为(-)。micro RNA-150的表达在增生性瘢痕和正常皮肤组织中的表达有统计学意义。原位杂交分析结果提示,micro RNA-150可能参与了增生性瘢痕的发生、发展,并随着增生性瘢痕的演进呈下降趋势。     

细胞周期素A在血管瘤组织中的表达及临床意义

目的 探讨细胞周期素A在血管瘤中的表达及与血管瘤发生、发展的关系。方法收集武汉大学人民医院病理科1996—2001年皮肤毛细血管瘤存档蜡块49例,所有标本常规HE染色和免疫组织化学SP法检测增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）,按Mulliken分类标准并结合PCNA的表达进行分组;然后采用免疫组织化学SP法和原位杂交检测49例皮肤毛细血管瘤增生期、退化期及正常皮肤组织中细胞周期素A的表达水平,并结合检测Ⅷ因子相关抗原的表达证实血管瘤组织中表达细胞周期素A的细胞的确是血管瘤内皮细胞,对免疫组织化学结果采用HPIAS-1000高清晰度彩色病理图文报告管理系统对细胞周期素A的表达进行定量分析。并用SPSS11．5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果增生期血管瘤内皮细胞中细胞周期素A高表达,退化期呈低表达。经q检验,增生期组与退化期组之间、增生期组与正常皮肤组之间,细胞周期素A的平均光密度及阳性面积率有显著性差异（P〈0．01）,退化期组与正常皮肤组之间平均光密度及阳性面积率的差异无显著性（P〉0．05）。结论细胞周期素A在增生期血管瘤组织中的过度表达使细胞周期紊乱,是增生期血管瘤内皮细胞不断分裂增生。     

TN—C与MDA-7在增生性瘢痕中表达与调控

增生性瘢痕是以皮肤损伤后成纤维细胞过度增殖为特征的一种病理改变,其发病机制尚不明确,目前没有有效的治疗方法。当皮肤组织损伤时,腱糖蛋白C（Tenascin-C,TN-C）具有多种不同的作用介导炎症和纤维化进程,并使组织有效修复。TN—C是细胞外基质中一个具有独特的六聚体结构的寡聚糖蛋白家族,TN—C一过性表达在器官形成期,在大多数成人组织不表达或表达极少。然而,在病理条件下TN—C表达增加,诸如炎症,伤口愈合和纤维化。TN—C参与胚胎形成、肿瘤发生及损伤修复过程有关,参与细胞黏附、增殖、迁徙、分化、细胞间相互作用以及细胞凋亡。黑色素瘤分化相关基因7／白介素24（MDA-7／IL-24）能选择性抑制瘢痕疙瘩中成纤维细胞的增殖,并诱导瘢痕疙瘩中成纤维细胞的凋亡,而对正常细胞无任何作用。MDA-7／IL-24很可能与瘢痕的形成有关。     

TN-C与MDA-7在增生性瘢痕中表达与调控

增生性瘢痕是以皮肤损伤后成纤维细胞过度增殖为特征的一种病理改变,其发病机制尚不明确,目前没有有效的治疗方法。当皮肤组织损伤时,腱糖蛋白C(Tenascin-C,TN-C)具有多种不同的作用介导炎症和纤维化进程,并使组织有效修复。TN-C是细胞外基质中一个具有独特的六聚体结构的寡聚糖蛋白家族,TN-C一过性表达在器官形成期,在大多数成人组织不表达或表达极少。然而,在病理条件下TN-C表达增加,诸如炎症,伤口愈合和纤维化。TN-C参与胚胎形成、肿瘤发生及损伤修复过程有关,参与细胞黏附、增殖、迁徙、分化、细胞间相互作用以及细胞凋亡。黑色素瘤分化相关基因7/白介素24(MDA-7/IL-24)能选择性抑制瘢痕疙瘩中成纤维细胞的增殖,并诱导瘢痕疙瘩中成纤维细胞的凋亡,而对正常细胞无任何作用。MDA-7/IL-24很可能与瘢痕的形成有关。     

巨噬细胞与树突状细胞在正常成人真皮内分布形式的研究

目的观察正常成人真皮内巨噬细胞和树突状细胞的分布、形态学和密度。方法正常人8例,取面部、躯干、四肢近端、四肢远端、手掌和足跖6个部位皮肤,进行纵行与水平切片。CD1a、CD68、OKM5单克隆抗体和FⅩⅢa多克隆抗体染色。结果CD1a和FXⅢa阳性细胞多位于皮肤附属器和血管周围。CD68阳性细胞在真皮浅层呈网状分布,真皮深层密度明显降低。各个部位的OKM5阳性细胞数较少。真皮内各个部位CD68阳性细胞高于相同部位CD1a、FⅩⅢa和OKM5阳性细胞(P<0·0001)。结论在真皮内存在大量的呈网状分布的CD68阳性的单核-巨噬细胞;同时在真皮,特别是浅层,有较多的树突状细胞,如郎格汉斯细胞和真皮树突状细胞,但其数量远低于CD68阳性的单核-巨噬细胞。CD68阳性的单核-巨噬细胞和真皮内的树突状细胞,是真皮内的主要防御细胞。     

Cyclin D1在人皮肤血管瘤不同时期的表达

目的　探讨cyclinD1蛋白在血管瘤发生、发展及退化过程中的表达状况及其意义。方法　采用免疫组织化学方法 (S P法 )检测人皮肤血管瘤增生期、退化期及正常皮肤组织中cyclinD1的表达水平 ,并结合第Ⅷ因子相关抗原的免疫组织化学染色证实表达cyclinD1的细胞是血管内皮细胞。利用计算机图像分析技术测量不同时期血管瘤组织和正常皮肤组织cyclinD1表达的平均光密度和平均阳性面积率。结果　增生期血管瘤内皮细胞cyclinD1表达水平高于退化期 ,差异有显著性 (P <0 0 5 ) ,退化期血管瘤内皮细胞cyclinD1表达水平与正常皮肤组织相比 ,差异无显著性 (P >0 0 5 )。结论　cyclinD1通过促进血管瘤内皮细胞增殖和血管生成而在血管瘤的形成过程中起重要作用。     

皮肤血管瘤组织中CHFR和PIK1的表达及意义

目的探讨CHFR和PIK1在人皮肤血管瘤组织中的表达及其意义。方法收集武汉大学人民医院病理科2008年-2011年皮肤毛细血管瘤存档蜡块40例,其中男性15例,女性25例。采用免疫组织化学S-P法检测40例皮肤血管瘤增生期、退化期及正常皮肤组织CHFR和PIK1表达水平,采用图像分析系统对CHFR和PIK1的表达进行定量分析,并用SPSS13.0软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验。结果 (1)CHFR的表达增生期血管瘤血管内皮细胞中可见少量的棕黄色颗粒,CHFR呈低表达,正常皮肤组及退化组血管内皮细胞中可见密集分布的棕黄色颗粒,CHFR呈高表达。增生期组CHFR的表达明显低于退化期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。(2)PIK1的表达增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,PIK1呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,PIK1呈低表达。增生期组PIK1的表达明显高于退化期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。结论 CHFR低表达促进了细胞周期,增强了细胞生长能力,与血管瘤的发生发展密切相关;在血管瘤增生期中,PIKl的表达水平上调,过量表达的PIK1会引起细胞的增殖,表明PIK1蛋白在血管瘤增生期中高水平表达与细胞的增殖是密切相关的。     

RTN4和TG2在增生期血管瘤组织中高表达及其临床意义

目的探讨RTN4和TG2在人皮肤血管瘤组织中的表达及其临床意义。方法收集武汉大学人民医院病理科2008年-2011年皮肤毛细血管瘤存档蜡块40例,其中男性15例,女性25例。采用免疫组织化学S-P法检测40例皮肤血管瘤增生期、退化期及正常皮肤组织RTN4和TG2表达水平,采用图像分析系统对RTN4和TG2的表达进行定量分析,并用SPSS13.0软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验。结果增生期组RTN4的表达明显高于退化期组和正常皮肤组,而后两组比较差异无统计学意义;增生期组TG2的表达明显高于退化期组和正常皮肤组,而后两组比较差异无统计学意义。结论 RTN4和TG2在增生期血管瘤组织中的表达明显高于正常皮肤组及退化组,提示RTN4和TG2在增生期血管瘤组织中表达上调,可能与瘤细胞的过度增殖,抗凋亡增强等有关。     

EPO/EPO-R、Bcl-2、Bax在皮肤血管瘤组织的表达及意义

目的研究促红细胞生成素(erythropoietin,EPO)和促红细胞生成素受体(erythropoietin-receptor,EPO-R)、B细胞淋巴瘤/白血病-2(B-cell lymphoma/Leukemia-2,bcl-2)、促凋亡基因在血管瘤不同时期的表达,探讨其意义及相互关联。方法采用免疫组织化学方法检测人皮肤血管瘤增生期、退化期及正常皮肤组织中EPO/EPO-R、Bcl-2、Bax的表达水平,利用计算机图像分析技术测量不同时期血管瘤组织和正常皮肤组织EPO/EPO-R、Bcl-2、Bax表达的平均光密度和平均阳性面积率。结果 1.EPO/EPO-R在增生期血管瘤内皮细胞的表达明显高于退化期血管瘤内皮细胞和正常皮肤组织血管内皮细胞(P0.01);EPO/EPO-R在退化期血管瘤内皮细胞的表达与正常皮肤组织血管内皮细胞相比,差异无显著性(P0.05)。2.Bcl-2在增生期血管瘤的表达明显高于退化期血管瘤和正常皮肤组织(P0.01);Bcl-2在退化期血管瘤的表达与正常皮肤组织相比,差异无显著性(P0.05)。3.Bax在退化期毛细血管瘤中表达高于增殖期和正常皮肤组织(P0.01),Bax在增殖期中表达高于正常皮肤组织(P0.05)。结论 Bcl-2可能是通过抑制内皮细胞的凋亡,使其增殖;Bax可能通过促进内皮细胞凋亡而抑制血管瘤的增生;EPO/EPO-R可能上调Bcl-2及下调Bax,改变Bcl-2与Bax比值,促进了内皮细胞的增殖。     

Expression and localization of insulin-like growth factor-1 in normal and post-burn hypertrophic scar tissue in human

The migration of epithelial cells from dermal appendages toward the wound surface is essential for re-epithelialization of partial thickness burn injuries. This study provides evidence that these cells in vivo synthesize a mitogenic and fibrogenic factor, insulin-like growth factor-1 (IGF-1), which may promote the development of the post-burn fibroproliferative disorder, hypertrophic scarring (HSc). An evaluation of 7 post-burn hypertrophic scars, 7 normal skin samples obtained from the same patients and 4 mature scars revealed that IGF-1 expressing cells from the disrupted sweat glands tend to reform small sweat glands of 4-10 cells/gland in post-burn HSc. The number of these cells increases with time and the glands become larger in mature scar. Other epithelial cells such as those found in sebaceous glands and basal and suprabasal keratinocytes, also express IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA obtained from whole skin and separated epidermis and dermis. However, cultured keratinocytes did not express mRNA for IGF-1. Histological comparisons between normal and HSc sections show no mature sebaceous glands in dermal fibrotic tissues but the number of IGF-1 producing cells including infiltrated immune cells was markedly higher in the dermis of hypertrophic scar tissues relative to that of the normal control. In these tissues, but not in normal dermis, IGF-1 protein was found associated with the extracellular matrix. By in situ hybridization, IGF-1 mRNA was localized to both epithelial and infiltrated immune cells. Collectively, these findings suggest that in normal skin, fibroblasts have little or no access to diffusible IGF-1 expressed by epithelial cells of the epidermis, sweat and sebaceous glands; while following dermal injury when these structures are disrupted, IGF-1 may contribute to the development of fibrosis through its fibrogenic and mitogenic functions. Reformation of sweat glands during the later stages of healing may, therefore, limit this accessibility, and lead to scar maturation.     

Fibronectin (FN) in hypertrophic scars and keloids

Summary Fibronectin (FN) distribution was compared among samples of normal human dermis, hypertrophic scar, keloid, and granulation tissues from deep injuries. Localization was established by use of fibronectin antibodies and the indirect immunofluorescence method. Fresh-frozen tissue was sectioned on a cryostat and examined by epifluorescence. Hypertrophic scar and keloid demonstrated heavy deposition of FN, which conformed to the nodular characteristics of the lesions. Intense localization occurred in granulation tissue over fibroblasts which were stellate and vesiculated, and over small blood vessels. FN-staining was weak in areas over fibroblasts which were more rounded and nonvesiculated. Staining for FN was also minimal over the collagen in normal dermis and the deeper, larger collagen fascicles in the lesions. Fibroblasts cultured from normal dermis, hypertrophic scar, and keloid for 5–6 weeks were intensely stained for FN. Extracellular matrix was heavily positive in cultures from the lesions compared with those from normal dermis.Supported in part by NIH Research Grant 1 R01GM 25159     

595nm 激光对兔耳瘢痕成纤维细胞增殖活性的影响

目的：探讨兔耳增生性瘢痕动物模型形成过程中成纤维细胞增殖活性的动态变化及595nm Vbeam激光照射的影响。方法：利用兔耳腹侧面建立增生性瘢痕模型,按不同时间段取材,采用免疫组织化学方法观察瘢痕形成不同时期增殖细胞核抗原（PCNA）蛋白的表达,对比研究在兔耳增生性瘢痕形成过程中595nm Vbeam激光照射对成纤维细胞增殖活性的影响。结果：上皮化后增殖细胞核抗原阳性细胞反应率随时间推移逐渐增高,至上皮化后4周达高峰。从上皮化后1周开始即可见到595nm Vbeam激光照射后增殖细胞核抗原蛋白表达较对照组明显减弱,成纤维细胞增殖活性受到明显抑制,两组差异具有极显著性（P〈0．01）。结论：595nm Vbeam激光照射可明显抑制兔耳增生性瘢痕成纤维细胞的增殖活性,对兔耳腹侧面增生性瘢痕有明显的防治作用。     

Bmi1在肝癌组织中的表达及其与细胞增殖和凋亡的关系

目的：探讨Bmi1在肝细胞肝癌（HCC）中的表达及与增殖和凋亡的关系。方法：收集HCC标本54例及相应的癌旁组织,10例正常肝组织标本,采用免疫组织化学EnVision二步法显示Bmi1的表达并结合增殖与凋亡特征进行分析。结果：在肝癌组织、癌旁组织细胞中Bmi1表达定位于胞核中,阳性表达率分别为79.6%（43/54）,31.2%（17/54）,10例正常肝组织未见表达,3组差异有统计学意义（P〈0.005）。HCC中Bmi1的高表达与年龄、性别、肿瘤大小、肿瘤数目、临床TNM分期、是否有肝硬化及是否有HBsAg感染无显著相关（P〉0.05）,但与组织学分级有关,高、中分化组Bmi1表达率显著高于低分化组（P〈0.05）。肝癌Bmi1阳性组增殖指数（PI）（50.3±21.4）%显著高于阴性表达组（17.3±7.1）%（P〈0.05）,凋亡指数（AI）无明显差异（P〉0.05）。结论：Bmi1在HCC中高表达,其表达增高可能与HCC的进展相关。     

A mathematical model for the simulation of the formation and the subsequent regression of hypertrophic scar tissue after dermal wounding

A continuum hypothesis-based model is presented for the simulation of the formation and the subsequent regression of hypertrophic scar tissue after dermal wounding. Solely the dermal layer of the skin is modeled explicitly and it is modeled as a heterogeneous, isotropic and compressible neo-Hookean solid. With respect to the constituents of the dermal layer, the following components are selected as primary model components: fibroblasts, myofibroblasts, a generic signaling molecule and collagen molecules. A good match with respect to the evolution of the thickness of the dermal layer of scars between the outcomes of simulations and clinical measurements on hypertrophic scars at different time points after injury in human subjects is demonstrated. Interestingly, the comparison between the outcomes of the simulations and the clinical measurements demonstrates that a relatively high apoptosis rate of myofibroblasts results in scar tissue that behaves more like normal scar tissue with respect to the evolution of the thickness of the tissue over time, while a relatively low apoptosis rate results in scar tissue that behaves like hypertrophic scar tissue with respect to the evolution of the thickness of the tissue over time. Our ultimate goal is to construct models with which the properties of newly generated tissues that form during wound healing can be predicted with a high degree of certainty. The development of the presented model is considered by us as a step toward their construction.     

MicroRNA 181b Regulates Decorin Production by Dermal Fibroblasts and May Be a Potential Therapy for Hypertrophic Scar

Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3’ un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β₁ stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β₁ induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.     

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

Background

Hypertrophic scars are pathologic proliferations of the dermal skin layer resulting from excessive collagen deposition during the healing process of cutaneous wounds. Current research suggests that the TGF-β/Smad signaling pathway is closely associated with normal scar and hypertrophic scar formation. TRAP-1-like protein (TLP), a cytoplasmic protein, has been reported to efficiently regulate Smad2- and Smad3-dependent signal expression in the TGF-β pathway. The relationship between TLP and Type I/III collagen (Col I/III) synthesis explored in the present study provides an effective target for wound healing and gene therapy of hypertrophic scarring.

Objective

To investigate the effects of TLP on collagen synthesis in human dermal fibroblasts.

Methods

Lentiviral vectors encoding TLP was constructed to transfect fibroblasts derived from normal human skin. The expression of Col I/III and phosphorylation of Smad2 and Smad3 in fibroblasts were examined after TLP treatment. In addition, the comparison of TLP expression in normal skin tissues and in hypertrophic scar tissues was performed, and the effect of TLP on cell viability was analyzed by MTT assay.

Results

TLP expression in hypertrophic scar tissue was markedly higher than in normal skin tissue. The Real Time PCR and Western blot test results both revealed that the synthesis of Col I/III was positively correlated with the expression of TLP. TLP also facilitate Smad2 phosphorylation while, conversely, inhibiting Smad3 phosphorylation. TLP may play a cooperative role, along with the cytokine TGF-β1, in improving the overall cell viability of skin fibroblasts.

Conclusions

TLP likely acts as a molecular modulator capable of altering the balance of Smad3- and Smad2-dependent signaling through regulation of phosphorylation, thus facilitating collagen synthesis in fibroblasts. Based on genetic variation in TLP levels in different tissues, these results suggest that TLP plays a key role in the process of TGF-β1/Smad3 signaling that contributes to wound healing and genesis of pathologic scars.     

Effects of platelet derived growth factor (PDGF) on fibronectin (FN) production by human skin and scar fibroblasts

The fibroblast-type cell found in hypertrophic scars and keloids demonstrates an elevated fibronectin (FN) production, compared to the same type of cell in normal dermis. We wished to determine if the effects of platelet derived growth factor (PDGF) on FN production in these cell types would be equivalent or different. Cell lines were established from the dermis (reticularis) of hypertrophic scars, keloids, uninvolved normal skin adjacent to the lesions, including an assumed normal skin adjacent to a keloid (AS), and normal skin from a different uninjured patient (DS). Each parent tissue from which the cell lines originated was diagnosed histologically. Each hypertrophic scar, keloid and normal adjacent skin, with one exception, showed typical histologic findings confirming the clinical diagnosis. DS was also normal. AS, although assumed to be normal, in fact, demonstrated portions of nodules from the adjacent keloid. All cell lines were grown under standard conditions with subconfluent cells metabolically labeled for radioimmunoassays measuring FN at passage 3 (8 to 9 weeks in culture) in the absence and presence of PDGF. Significant differences in production of FN/cell and FN/PR/cell between two hypertrophic scars and their matched normal skins and for one keloid and its matched normal skin were observed. However, no significant difference was observed between the other keloid and AS, nor between the other hypertrophic scar and DS. PDGF significantly stimulated FN production in 2 of 4 NS cell lines, and in the AS cell line. By FN/cell values, 2 of 5 cell lines from the lesions were inhibited and one was increased. In terms of FN/PR/cell, 1 of 5 cell lines from the lesions was stimulated and the others showed no differences. The mixed results may be attributable to the likelihood that the cell lines represent mixed populations. This study demonstrates the importance of: 1) histological characterization of all parent tissues from which cell lines are derived, and 2) matching cell lines from lesions with cell lines from uninvolved normal dermis, in the same individual.     

Therapeutic effects of liposome-enveloped Ligusticum chuanxiong essential oil on hypertrophic scars in the rabbit ear model

Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-β(1)). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β(1), MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.     

Effect of Mederma on hypertrophic scarring in the rabbit ear model

Currently accepted conservative treatments of hypertrophic scars are limited to steroid injections, radiation therapy, and silicone occlusive therapy. However, the use of Mederma for these problematic lesions has become quite prevalent in the clinical setting. Little scientific evidence exists to support the efficacy of this product in reducing hypertrophic scars. The aim of this study was to study the effects of Mederma on hypertrophic scars in the rabbit hypertrophic scar model, allowing the histologic quantification of scar elevation, dermal collagen organization, vascularity, and inflammation and the gross examination of scar erythema. Full-thickness wounds down to cartilage, four per ear, were created in four New Zealand White rabbits, for a total of 32 scars. Twenty-eight days after the initial wounding, the hypertrophic scars were photographed, and treatment of half of the scars on each ear was begun with Mederma three times per day for a total of 4 weeks. The untreated scars served as control scars and were left exposed to air. After 4 weeks of treatment, the scars were once again photographed. The rabbits were then killed, and the scars were analyzed histologically. The pretreatment and posttreatment photographs were compared by using computer quantification of magenta, yellow, and cyan expression within the scars.Histologic analysis demonstrated no significant reduction in scar hypertrophy or scar elevation index. However, a significant improvement in dermal collagen organization was noted on comparing Mederma-treated scars with untreated control scars (p < 0.05). No significant difference in dermal vascularity or inflammation was noted. Computer analysis of the scar photographs demonstrated no significant reduction in scar erythema with Mederma treatment. The active product in Mederma, allium cepa, has as its derivative quercetin, a bioflavonoid noted for its antiproliferative effects on both normal and malignant cells, and its antihistamine release effects. These properties could theoretically prove beneficial in reversing the inflammatory and proliferative responses noted in hypertrophic scars. Despite the authors' inability to demonstrate a reduction in scar hypertrophy, the improvement in collagen organization noted in the Mederma-treated scars suggests it may have an effect on the pathophysiology of hypertrophic scar formation.