病理性瘢痕中结缔组织生长因子的免疫组化研究

目的：研究结缔组织生长因子在病理性瘢痕组织中的表达,以探讨其与病理性瘢痕形成的关系。方法：分别留取正常皮肤15例,浅表性瘢痕20例,增生性瘢痕、增生性瘢痕边缘正常皮肤、瘢痕疙瘩及瘢痕疙瘩边缘正常皮肤各20例组织标本,应用HE染色、免疫组化（SABC法）染色,观察CTGF在各组织中的表达,并用图像分析系统定量分析其在不同组织中表达水平的差异性。结果：CTGF在增生性瘢痕、瘢痕疙瘩、瘢痕疙瘩边缘正常皮肤中的表达均明显高于正常皮肤,有显著性差异（P〈0.05）;而在浅表性瘢痕、增生性瘢痕边缘正常皮肤中仅有极微弱的CTGF阳性着色,与正常皮肤相比差异无统计学意义（P〉0.05）。免疫组化研究显示CTGF主要定位于真皮层成纤维细胞胞浆中。结论：结缔组织生长因子与病理性瘢痕临床生物学行为之间有相关性,在其发病过程中可能发挥重要作用,可能成为今后临床治疗瘢痕的一个有力靶位。     

病理性瘢痕中结缔组织生长因子的免疫电镜观察

目的：研究结缔组织生长因子（CTGF）在病理性瘢痕组织中的表达定位，以探讨其在病理性瘢痕中的作用及与病理性瘢痕形成的关系。方法：分别留取正常皮肤2例、浅表性瘢痕3例、增生性瘢痕、增生性瘢痕边缘正常皮肤、瘢痕疙瘩及瘢痕疙瘩边缘正常皮肤各5例组织标本，用特异性抗体作为标记物，用胶体金作示踪物进行免疫电镜观察，观察标记物所在位置，以了解在不同组织中表达水平的差异性。结果：CTGF在增生性瘢痕、瘢痕疙瘩、瘢痕疙瘩边缘正常皮肤中的表达均明显高于正常皮肤、浅表性瘢痕及增生性瘢痕边缘正常皮肤。免疫电镜标记显示成纤维细胞细胞超微结构清晰，金颗粒呈团状、点灶状分布，特异性强，CTGF蛋白阳性标记主要位于粗面内质网，粗面内质网核糖体、胶原纤维、细胞外基质、桥粒连接、常染色质等部位也有表达。结论：CTGF与病理性瘢痕的形成有相关性，在其发病过程中可能发挥重要作用。     

P53 Immunohistochemical Expression in Early Posttransplant-Associated Malignant and Premalignant Cutaneous Lesions

Background.  Current evidence suggests that p53 accumulation is critical to the development of skin cancer in the general population. It is possible, however, that the molecular steps involved in transplant-associated and non-transplant-associated skin carcinogenesis may differ.
Objective.  Our purpose was to examine p53 expression in premalignant and malignant skin lesions from renal transplant recipients (RTRs) in their first 3 years of immunosuppression, as well as in equivalent lesions from immunocompetent normal individuals.
Methods.  p53 expression was examined by routine immunohistochemical methods using the anti-p53 monoclonal antibody DO7.
Results.  p53 immunoreactivity was more prevalent in dysplastic epidermal keratoses and cutaneous carcinomas from RTRs than in equivalent lesions from nontransplant controls. Statistical analysis revealed significant differences, however, only in premalignant skin lesions ( p = 0.03).
Conclusion.  This study demonstrates that accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of RTRs, and that this may occur as an early step in transplant-associated skin carcinogenesis.     

Naturally acquired anti-alpha Gal antibodies in a murine allograft model similar to delayed xenograft rejection

Abstract: Antibodies directed against galactose‐α1,3‐galactose (αGal) are believed to play an important a role in the pathogenesis of delayed xenograft rejection (DXR). This study was designed to determine whether α1,3‐galactosyltransferase‐deficient (Gal KO) mice can naturally acquire a sufficient anti‐αGal titre to cause the delayed type rejection of αGal‐expressing hearts. Gal KO mice of various ages were assessed for anti‐αGal antibody levels. αGal‐expressing hearts were transplanted heterotopically into these mice and monitored daily. Rejecting and surviving hearts were evaluated histologically. Results: in Gal KO mice greater than 6‐month‐old, 64% had an anti‐αGal antibody titre above the background level. When wild‐type αGal‐expressing hearts were transplanted into this group, 45% of grafts rejected within 5 to 13 days. Histological examination of the rejected hearts displayed marked tissue damage and an inflammatory infiltrate of predominantly macrophage/monocytes. Surviving grafts showed preserved morphology. Like humans, Gal KO mice naturally develop anti‐αGal antibodies with age. The titre in these mice was sufficient to cause a "delayed‐type" rejection of a significant proportion of αGal‐expressing cardiac grafts. This model thus provides an opportunity to investigate the role of naturally acquired anti‐αGal antibodies in the pathogenesis of DXR.     

Human and non-human primate anti-galactosyl response after injection of rat monoclonal antibody bearing galactosyl epitopes

Abstract: In the case of clinical use of pig‐to‐human xenografting, any exogenous source of α‐galactosyl epitopes will elicit an anti‐galactosyl immune response, which could be deleterious for the xenograft. The presence of Galα(1–3)Gal residues was thus examined by western blotting on various rat monoclonal antibodies (mAb), which are used in clinical trials. In parallel, the anti‐galactosyl humoral response was assessed in the serum of kidney allograft recipients and experimental baboons, which received these mAbs. Galactosyl residues were evidenced on all rat monoclonal antibody tested. The anti‐galactosyl response was weak in kidney allograft recipients receiving a basic immunosuppression (Cyclosporine, Azathioprine, Prednisolone) and iterative injections of rat mAbs. In contrast, untreated or immunosuppressed baboons that received rat mAbs developed a major anti‐galactosyl humoral response. These results suggest that anti‐galactosyl sensitization produced by therapeutic agents will have to be considered in the case of clinical xenotransplantation.     

Analysis of differences of gene expressions in keloid and normal skin with the aid of cDNA microarray

Background: Microarray analysis is a popular tool to investigate the function of genes that are responsible for the phenotype of the disease. Keloid is a intricate lesion which is probably modulated by interplay of many genes. We ventured to study the differences of gene expressions between keloids and normal skins with the aid of cDNA microarray in order to explore the molecular mechanism underlying keloid formation. Methods: The PCR products of 8400 human genes were spotted on a chip in array. The DNAs were then fixed on the glass plate by a series of treatments. Total RNAs was isolated from freshly excised human keloids and normal skin, and then was purified to mRNA by Oligotex. Both the mRNA from keloids and normal skin was reversely transcribed to cDNAs with the incorporations of fluorescent dUTP, for preparing the hybridization probes. The mixed probes were then hybridized to the cDNA microarray. After highly stringent washing, the cDNA microarray was scanned for the fluorescent signals to display the differences between two kinds of tissues. Results: Among 8400 human genes, there were 402 genes (4.79%) with different expression levels between the keloids and normal skins in all cases, 250were up-regulated (2.98%) and 152 down-regulated (1.81%). Analyses of collagen, fibronectin, proteoglycan,growth factors and apoptosis related molecule gene expression confirmed that our molecular data obtained by cDNA microarray were consistent with published biochemical and clinical observations of keloids. Conclusions: DNA microarray technology is an effective technique in screening for differences in gene expression between keloid and normal skin. Many genes are involved in the formation of keloids. Further analysis of the obtained genes will help understand the molecular mechanism of keloid formation.     

Human serum induces apoptosis of xenogenic cardiomyocytes in vivo and in vitro

Abstract: Discordant xenotransplantation is complicated by delayed xenograft rejection (DXR). Previous studies have demonstrated that anti‐apoptotic genes are protective against DXR. This study examines the hypothesis that apoptosis plays a role in human anti‐xenograft responses. C57BL/6 mice and NOD SCID mice were given a single intravenous injection of either a lethal dose (LD, survival < 30 min) or a sublethal dose (SLD) of human serum, and isolated pig and mouse rod‐shaped cardiomyocytes were exposed to human serum in vitro. In situ detection of apoptotic cells in mouse hearts was assessed using a terminal deoxynucleotidyl transferase‐mediated dUTP nicked‐end labeling assay. Mice transfused with human serum had approximately a 10‐fold increased percentage of apoptotic cells after SLD 18 h post‐injection compared with animals given saline, and a fourfold increase over LD. Administration of cobra venom factor (CVF) decomplemented SLD 18 h did not significantly ( P  > 0.05) alter the percentage apoptosis. The addition of 20 mM Gal‐α‐1,3‐Gal to SLD 18 h significantly ( P  < 0.05) reduced percentage apoptosis to levels comparable to saline treated control animals. In vitro using mouse and pig cardiomyocytes demonstrated parallel results as in vivo experiments.
Human serum induces apoptosis of cardiomyocytes in immunocompetent and immunoincompetent mice in vivo, as well as mouse and pig cardiomyocytes in vitro. Further, this apoptotic response can be inhibited by the addition of Gal‐α‐1,3‐Gal without affecting the capacity of the serum to cause HAR. These results demonstrate that a putative human serum factor induces a delayed apoptotic injury of xenograft tissues, and supports the hypothesis that apoptosis may be an important mediator of DXR.     

Removal of xenoreactive antibodies by protein-A immunoadsorption: experience in 22 patients

Abstract: The presence of naturally occurring anti‐Galα1–3Gal (antiαGal) Ab in human serum is believed to be a major factor in the pathogenesis of hyperacute rejection of discordant organ xenografts such as the pig‐to‐human combination. Galα1–3Gal epitopes are expressed on pig tissues and the binding of anti‐Galα1–3Gal leads to endothelial cell activation and complement‐mediated hyperacute graft rejection. Several strategies have been suggested in donor animals or in the xenograft recipient to overcome the anti‐αGal barrier. Protein‐A immunoadsorption (PAIA) was developed for the in vivo removal of circulating Ab and it has been shown to be effective in cases where pathogenic auto or alloAb are present. The aim of our study was to analyze the effect of PAIA on total and xenoreactive serum anti‐αGal immunoglobulin levels in a group of patients treated with this technique for different diseases. After three consecutive sessions of PAIA, total and xenoreactive IgG and IgM immunoglobulin levels were decreased by more than 50% of pre‐treatment levels. So we conclude that PAIA is an effective method to significantly reduce circulating Ab, including xenogeneic IgM and IgG Ab. This mode of therapy might be considered as a tool to overcome hyperacute xenograft rejection. PAIA combined with other therapeutic approaches may well protect the xenograft.     

核心蛋白聚糖和光蛋白聚糖在体外培养的瘢痕疙瘩成纤维细胞中的表达

目的:研究体外培养的瘢痕疙瘩成纤维细胞中两种小分子蛋白聚糖(核心蛋白聚糖和光蛋白聚糖)的表达水平,探讨这两种蛋白聚糖与瘢痕疙瘩发生机制的关系。方法:采用实时PCR(Real-timePCR)和WesternBlot方法,研究体外培养的瘢痕疙瘩和正常皮肤成纤维细胞中核心蛋白聚糖和光蛋白聚糖的mRNA和蛋白表达水平,并进行比较分析。结果:不同患者来源的瘢痕疙瘩成纤维细胞中核心蛋白聚糖的mRNA表达水平差异较大,最高表达水平是最低表达水平的5.6倍。瘢痕疙瘩和正常皮肤的培养成纤维细胞中,核心蛋白聚糖和光蛋白聚糖在基因和蛋白表达水平上无显著性差异。结论:核心蛋白聚糖和光蛋白聚糖在体外培养的单层瘢痕疙瘩和正常皮肤成纤维细胞中的表达无特异性改变,它们在瘢痕疙瘩形成过程中所起的作用尚有待进一步研究。     

瘢痕疙瘩中Smads表达的研究

目的 探讨不同类型Smads在瘢痕疙瘩、正常瘢痕和正常皮肤中的差异表达及其意义.方法 采用RT-PCR和Western Blot法分别对10例瘢痕疙瘩、10例正常瘢痕及10例正常皮肤组织,以及体外培养瘢痕疙瘩、正常瘢痕及正常皮肤成纤维细胞中的Smads mRNA及蛋白的表达水平进行检测.用t检验比较其表达差异,P<0.05为差异具有统计学意义.结果 在瘢痕疙瘩组织及瘢痕疙瘩成纤维细胞中,Smad7的mRNA及蛋白水平表达明显低于正常瘢痕(P<0.05)和正常皮肤(P<0.05),而Smad2、3的mRNA及蛋白水平表达以及磷酸化的Smad2、3的蛋白水平表达并无明显改变(P>0.05).结论 在瘢痕疙瘩中,存在有Smad7的表达缺陷,这可能是增高的转化生长因子-β1(TGF-β1)/Smads信号传导不能被自身负反馈循环终止的重要原因.     

病理性瘢痕中结缔组织生长因子基因的表达

目的　探讨结缔组织生长因子在增生性瘢痕和瘢痕疙瘩发病机制中的作用。　方法　分别留取正常皮肤 5例、增生性瘢痕 15例和瘢痕疙瘩 7例组织标本 ,测定组织中羟脯氨酸含量 ,通过逆转录 -聚合酶链反应 (RT- PCR)和图像定量分析 ,检测组织中结缔组织生长因子基因表达水平。　结果　正常皮肤、增生性瘢痕和瘢痕疙瘩组织中羟脯氨酸含量分别为 (2 6 .5 2± 4 .10 )、(84 .10± 1.76 )和 (92 .38± 2 .0 4 )μg/ mg,后两者与前者比较差异有统计学意义 (P<0 .0 1) ;正常皮肤、增生性瘢痕和瘢痕疙瘩组织中结缔组织生长因子 m RNA指数分别为 0 .0 9± 0 .2 5、0 .78± 0 .6 3和0 .84± 0 .0 4 ,后两者与前者比较差异有统计学意义 (P<0 .0 1)。　结论　结缔组织生长因子在增生性瘢痕和瘢痕疙瘩纤维化进程中可能起着促进作用。     

The target antigens of naturally occurring human anti-beta-galactose IgG are cryptic on porcine aortic endothelial cells

Abstract: The identification of the xeno‐antigens/xeno‐antibodies combinations involved in pig‐to‐human xenograft rejection is an essential step for understanding this process and for the development of procedures to prevent it. Although it is widely accepted that the terminal disaccharide Galα1,3Gal‐R is by far the major epitope recognized by human natural antibodies reactive with pig tissues, there is also evidence that other carbohydrates epitopes might be important in xenograft rejection.
In an attempt to further improve our knowledge of the repertoire of human natural antibodies with anti‐pig specificity we sought to determine whether naturally occurring human anti‐β‐galactose IgG could interact with porcine aortic endothelial cells (PAEC). Histochemical analysis of porcine aorta sections revealed that the carbohydrate structures recognized by the anti‐β‐galalactose IgG are present on endothelial cells but in a cryptic form that can be unmasked by sialidase treatment. These structures were also found to be cryptic in cultured PAEC. In addition we demonstrated that PAEC may adsorb fetal calf serum (FCS) glycoproteins when cultured in FCS‐supplemented medium, a process susceptible to generating artifactual observations in carbohydrate antigens analysis.
In conclusion, despite their abundance, human anti‐β‐galactose IgG do not represent a primary concern in pig‐to‐human xenotransplantation as the carbohydrate structures to which they bind are normally masked by sialic acid residues on porcine endothelial cells. However, whether these cryptic epitopes might be exposed on endothelial cells from genetically engineered animals should be further investigated because, if so, additional approaches will be needed to suppress their interaction with human anti‐β‐galactose IgG.     

增殖瘢痕成纤维细胞接触后增殖及生物合成特性对异常瘢痕形成的机理

目的 为明确不同异常瘢痕成纤维细胞在体外完全接触后其增殖活性及生物全成功能的特性。方法 以瘢痕疙瘩、增生性瘢痕和正常皮肤（各6例）为材料，通过细胞培养、免疫组织化学及分子生物学等方法，对不同成纤维细胞在细胞接触及未接触时通过检测增殖细胞核内抗原、P16、Ⅰ、Ⅲ型胶原蛋白及前胶原基因表达对成纤维细胞的增殖、抑制及生物合成进行了研究。结果 瘢痕疙瘩成纤维细胞接触表现为细胞交叉重叠及较高的增殖活性及旺盛的生物合成功能，提示其失去了接触性抑制及密度抑制。皮肤成纤维细胞接触后则增殖及生物合成功能明显下降。增生性瘢痕成纤维细胞接触后表现为旺盛的生物合成功能，但其增殖活性处于瘢痕疙瘩和正常皮肤成纤维细胞之间。结论 不同瘢痕成纤维细胞接触后增殖及生物合成的特性可能是形成不同瘢痕的机理之一。     

病理性瘢痕中结缔组织生长因子的表达及其意义

目的:观测结缔组织生长因子(Connective Tissue Growth Factor,CTGF)在瘢痕组织中的表达,以探讨其与病理性瘢痕形成的关系。方法:分别取正常皮肤20例、成熟瘢痕20例、增生性瘢痕20例和瘢痕疙瘩20例标本,经HE染色、原位杂交(SABC法)染色,用图象分析系统定量分析CTGF在不同组织中表达的差异性。结果:CTGF在增生性瘢痕、瘢痕疙瘩、瘢痕疙瘩边缘正常皮肤中呈强阳性表达,明显高于其在正常皮肤中的表达,差异具有统计学意义(P<0.05);其在成熟瘢痕、增生瘢痕边缘正常皮肤呈弱阳性表达,与正常皮肤相比差异无统计学意义(P>0.05)。结论:CTGF在病理性瘢痕的发生发展中起重要作用。     

Effects of an Inhibitor of Nitric Oxide Synthesis on Skin Wound Repair

Introduction:  The aim of this study was to compare the effects of Urgotul^® and other greasy dressings and interfaces on normal human dermal fibroblasts (NHDF) monolayers in vitro . The selected end points were the cell proliferation, the morphology of the extracellular matrix (ECM) upon dressing removal, and the structure of the underlying fibroblasts.
Materials and methods:  Equivalent pieces of each dressing were applied on NHDF monolayers for different times. Cell proliferation was measured via [3H] thymidine incorporation. Identical cultures were used to assess the dressing impact on the morphology of cells in culture after MTT staining and micro‐photographing. ECM morphology was shown by immunoflorescence, using an anticollagen I antibody. Effects on cell ultrastructure were documented by confocal laser microscopy after tubulin/actin double labelling.
Results:  Among the five tested greasy dressings and interfaces, only Urgotul^® showed a stimulating effect on the proliferation of NHDF. Two dressings did not modify proliferation and two other had cytostatic effects.
In addition, the lesions of the ECM upon dressing removal were clearly the lowest with Urgotul^®(low adherence to cellular surface and/or to extracellular matrix). The ultrastructure of the NHDF in direct contact with Urgotul^® was not significantly modified.
Conclusion:  Fibroblasts are the key cells of wound healing. The use of nonaggressive greasy gauzes and/or interfaces promoting cell proliferation should be of interest. Clinical evaluations are required to confirm these in vitro results.     

Expression of two isozymes of acyl-coenzyme A: Cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma

Objectives:   The present study investigated the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) and -2 in clear cell type renal cell carcinoma (RCC).
Methods:   Clear cell type RCC and corresponding normal kidney tissue samples were obtained from 19 surgical cases (28–85 years of age). Tissue extracts were assayed for ACAT activity and protein expression by immunoblotting with anti-ACAT-1 and anti-ACAT-2 antibodies. Frozen sections were subjected to Oil red O staining for lipids, and were immunostained with ACAT-specific antibodies.
Results:   Acyl-coenzyme A cholesterol acyltransferase activity was 5.7-fold higher ( P  < 0.01) in clear cell carcinoma (23.52 ± 4.90 pmol/mg protein/min) than in normal kidney (4.12 ± 0.36). Consistent with this, immunoblotting and immunohistochemical staining revealed strong expression of ACAT-1 in clear cell type RCC. Densitometric analysis showed that ACAT-1 expression was 2.9-fold higher in clear cell type RCC than in normal kidney. In contrast, ACAT-2 expression was negative in clear cell type RCC and normal kidney. Oil red O staining showed massive deposits of lipid in RCC cells.
Conclusions:   We identified strong expression of ACAT-1 in clear cell type RCC. Upregulation of ACAT-1 leads to high ACAT enzymatic activity, which accelerates the accumulation of cholesterol ester in clear cell type RCC.     

Dispersion of Pressure to the Head in Brain/NeuroSurgery

Skin and soft tissue defects are sometimes problematic especially when the defects large, contaminated, irradiated, or poor blood supplied. The human mesenchymal stem cells (hMSCs) are proliferated upon basic fibroblast growth factor (bFGF) stimuli in vitro and in vivo. In this experiment, the skin and soft tissue defects are investigated if the wounds are able to be reepithelialized or accelerated by hMSCs, bFGF and porcine‐derived bilayered skin template.
1.5 × 1.5 cm² nude rat skin and soft tissue defects including panniculus carnosus are excised and 1 × 10⁶ hMSCs and various doses of bFGF (1–100 μg) applied. Before and after normal reepithelialization, the tissues are tested for protein expressions by immunohistochemistry and Western blotting.
The wound sizes are significantly decreased at day 7 with hMSCs with 1, 10, or 100 μg bFGF compared to hMSCs‐alone or medium‐only. All the wounds healed by day 42. 42 Kda and 38 Kda human‐derived pancytokeratin expressions, which do not cross‐react with murine antigens, by Western blotting significantly augmented by 10 μg bFGF compared to hMSCs‐alone. The epidermal immunolocalizations such as integrin α3 and SKALP (Skin‐derived Anti Leukoproteinase) are greatly elevated in time and dose‐dependent manner. Human pan‐cytokeratin expressions are immunoreactive even at day 42.
These data suggest the skin and soft tissue wound healing is accelerated by hMSCs together with bFGF, partly by means of differentiation of hMSCs toward epidermal components.     

Preventive Effect of Fibroblast Growth Factor and Hepatocyte Growth Factor on Ceramide‐Induced Dysfunction Human Small Intestinal Cells

Aim:  To investigate whether TNF‐ is necessary for hepatocyte proliferation, we study liver regeneration after partial hepatectomy in mice lacking TNF receptor‐1.
Methods:  TNF receptor type‐1 knockout mice and wild‐type mice were subjected to two‐thirds partial hepatectomy (PHx). Liver regeneration was evaluated by assessing liver weights and Ki67 immunohistochemistry. Riken cDNA microarray analysis was performed on liver samples from mice undergoing PHx to compare clearly differentiated mouse PHx models (TNFR‐1 knockout mice‐K group, and wild type mice‐W group).
Results:  The cumulative survival after PHx in K group was lower than in W group. The mortality rate in K group during the first 3 days after PHx was higher (33%) than in W group. The time to regain the liver weight in K group was 14 days and 7 days in W group. The plasma IL‐6 levels in K type at 3 hr was significantly higher than in W group. The Ki67 expression in K group at 4 days was lower than in W group. LPS, Toll like receptor 4 precursor and MAPK 8 interacting protein in K group was higher than in W group. For cell cycle‐regulated genes, cyclin D1, NFB light chain and TNF receptor super family membrane 1a in K group was lower than in W group.
Conclusions:  Lack of TNF‐ signaling through TNF receptor type 1 suppresses liver regeneration after partial hepatectomy in spite of enhancement of LPS–JNK pathway, no TNF‐a and IL‐6 pathway.     

细胞信号传导在激素和干扰素诱导的增殖瘢痕成纤维细胞凋亡中的作用

目的 探讨对瘢痕疙瘩和增生性瘢痕成纤维细胞在激素和干扰素α-2b(IFNα-2b)作用后是否产生凋亡,以及相关细胞信号传导通路的激活或抑制是否一致.方法 对6例瘢痕疙瘩、增生性瘢痕及6例皮肤标本,采用细胞培养、免疫组织化学、凝胶电泳及FACE ELISA方法通过检测Bax和Bcl-2蛋白表达、特异性DNA梯状条带以及激活(磷酸化)的ERK1/2和JNK的吸光度A值,对不同成纤维细胞在地塞米松(0.1 mg/ml)和干扰素α-2b(1000U/ml)作用后的细胞凋亡及相关细胞信号传导通路进行了研究.结果 地塞米松可通过激活ERK1/2和JNK细胞传导通路诱导三类不同来源成纤维细胞发生细胞凋亡;干扰素α-2b不能诱导这三类不同来源成纤维细胞发生明显细胞凋亡,且IFN α-2b抑制增殖瘢痕的ERK1/2通路,而对JNK通路无影响,其不引起正常皮肤成纤维细胞ERK1/2和JNK通路的变化.结论 激素类药物和干扰素α-2b对瘢痕疙瘩、增生性瘢痕和正常皮肤成纤维细胞的作用机制不同.