基因芯片技术在增生瘢痕研究中的应用

创伤愈合伴随瘢痕形成。成纤维细胞（fibroblast，Fb）过度生长增殖，细胞外基质（extracellular matrix，ECM）局部过量堆积则可形成高于皮肤表面的过度增生性瘢痕，包括增生性瘢痕（hypertrophic scar，HS）和瘢痕疙瘩（keloid，K）。发生HS或K的患者可有身体机能受限，生活质量受到严重影响。关于HS和K的病理机制研究很多，但具体机制还不清楚。有关瘢痕相关基因的研究报道已有一些，尤其是单个基因的报道为多。     

病理性瘢痕形成的细胞分子生物学研究

病理性瘢痕包括增生性瘢痕(Hypertrophic Scar,HS)和瘢痕疙瘩(Keloid,K),是因成纤维细胞增殖,生长失控、胶原过度沉积导致真皮纤维化。K表现为侵袭性瘤样生长,而HS却随时间推移有自然软化趋势,可见在形成机制方面还有不同之处。虽然目前病理性瘢痕形成的机制还不太清楚,但这方面的研究却方兴未艾,本文就近年来对病理性瘢痕发生机制的研究综述如下。1病理性瘢痕形成的机制研究1.1肌成纤维细胞在瘢痕形成中的作用:正常创面愈合过程中的创面收缩或过度愈合引起的病理性瘢痕以及各种纤维化疾病中,肌成纤维细胞(Myofibroblast,MFB)的作用越…     

信号转导与病理性瘢痕

病理性瘢痕包括增生性瘢痕（hypertrophic scar,HS）和瘢痕疙瘩（keloid,K）,是人体对创伤产生过度愈合反应的结果,它们都以成纤维细胞（fibroblast,FB）增殖旺盛并分泌大量细胞外基质,导致胶原的过量合成和沉积为特征。病理性瘢痕作为整形外科的常见疾病,一直是国内外学者研究的热点,其研究报道每年以50%的速度增长。     

人参皂苷Rg3抗肿瘤作用与病理性瘢痕关系研究进展

瘢痕是创伤愈合的必然结果。伤口愈合有两种方式,一种是完全修复,即与原来损伤组织结构相同的细胞和组织修复,或是伤口上皮化最后以瘢痕性愈合而告终,这种瘢痕属于正常瘢痕;另一种修复是以胶原为主的细胞外基质成分的大量沉积,称为病理性瘢痕（Abnormal Scar,AS）,包括增生性瘢痕（Hypertrophic scar,HS）和有肿瘤样生长倾向的瘢痕疙瘩（Keloid）。     

病理性瘢痕基因治疗的研究进展

病理性瘢痕一直是整形外科治疗中的一个难题，是真皮组织过度增生及细胞基质成分大量沉积的结果，表现为高出皮肤表面并影响外观与功能的异常增生，也称为异常瘢痕。临床上分为增生性瘢痕（hypertrophic scar，HS）及瘢痕疙瘩（keloid,K），目前尚无理想的治疗方法。笔者现从基因治疗的角度出发。探讨病理性瘢痕基因治疗的研究进展及前景。     

TGF-β与增生性瘢痕相关性的研究进展

瘢痕(scar)从病理学上可分为正常瘢痕(normal scar)和病理性瘢痕(abnormal scar)。以病理性瘢痕最多见[1],主要包括增生性瘢痕(hypertrophic scar,HS)和瘢痕疙瘩(keloid,K)。HS是由创伤、炎性反应等引起,以成纤维细胞(Fibroblast,Fb)增殖失控和胶原等大量细胞外基质(Extra cellular matrix,ECM)过度产生和沉积为特征的人类真皮区特有的纤维代谢性疾病[2-4],     

病理性瘢痕的研究进展

增生性瘢痕(hypertrophicscar，HS)和瘢痕瘩(keloid，K)是特发于人类的病理性瘢痕，是整形外科的常见疾病，也是长期以来国内外学者研究的难点和重点。近年来，随着研究的不断深入，国内外学者对病理性瘢痕的研究取得了较大的进展。笔者现对本期的瘢痕研究栏目中所涉及的关于病理性瘢痕研究的几个问题加以评述，希望对病理性瘢痕研究的进一步深入提供帮助。     

病理性瘢痕的基础理论研究及治疗现状

病理性瘢痕包括增生性瘢痕(HS)和瘢痕疙瘩(K)，是继发于创伤愈合的一系列复杂的病理生理过程，是皮肤损伤后组织过度增生修复的结果。病理性瘢痕是由于以成纤维细胞为主的细胞增殖、活性增强、过度合成胶原、纤维连接蛋白及糖蛋白，打破了细     

细胞周期蛋白D1和p16与病理性瘢痕关系的研究进展

增生性瘢痕（hypertrophic scar，HS）和瘢痕疙瘩是最常见的病理性瘢痕，多由创伤引起，形成机制目前尚不十分清楚。多数学者认为，成纤维细胞（Fb）异常增殖是瘢痕增生和持续存在的主要原因，其生长特性及增殖活性与细胞周期关系密切。调控细胞周期最主要的一对正、负调节因子——细胞周期蛋白（cyclin）D1和p16成为人们研究的热点。     

树突状细胞在异常瘢痕中的免疫调控作用

目的探讨树突状细胞与异常瘢痕发病机理的关系.方法采用免疫组织化学方法检测6例增生性瘢痕(HS)、6例瘢痕疙瘩(K)和6例正常皮肤DC表面分子HLA-DR和CD1a的含量,并观察激素对HSHA-DR和CD1a的影响.结果①HS和K组织中表皮HLA-DR+DC的数量(806.67±101.72)个/mm2和(870.00±134.24)个/mm2,明显高于正常皮肤(P＜0.05),HLA-DR分子在角质形成细胞和成纤维细胞中异常表达.②HS和K组织中表皮CD1a+DC的数量(700.00±97.23)个/mm2和(780.00±104.47)个/mm2/明显高于正常皮肤(P＜0.05).③激素治疗3,7d时,HS表皮HLA-DR+DC的数量(476.67±70.02)个/mm2和(447.76±90.03)个/mm2,CD1a+DC的数量(456.36±82.88)个/mm2和(396.18±99.36)个/mm2,明显降低(P＜0.05).结论①HLA-DR和CD1a分子表达量增加,提示HS和K局部组织可能处于高免疫应答状态;②激素可能通过抑制HLA-DR和CD1a分子的表达量降低HS高免疫应答状态.     

增生性瘢痕和瘢痕疙瘩中PTK活性测定

目的测定增生性瘢痕和瘢痕疙瘩组织中PTK活性变化,探讨PTK在瘢痕形成中的作用。方法利用活化的PTK催化底物多肽磷酸化,再计数底物中掺入32P的放射活性的原理,测定增生性瘢痕、瘢痕疙瘩、成熟瘢痕和正常皮肤组织中PTK活性。结果增生性瘢痕和瘢痕疙瘩组织中PTK的活性显著高于正常成熟瘢痕和正常皮肤（P＜0.001,分别高出正常皮肤150.80%和313.80%）,瘢痕疙瘩高于增生性瘢痕（P＜0.001,高出65.01%）而成熟瘢痕和正常皮肤间没有差异（P＞0.05）。结论瘢痕组织中PTK活性升高且与增生程度相关,PTK介导生长刺激的信号转导使细胞增殖和合成物质的功能增强而发生瘢痕增生。     

增生性瘢痕和瘢痕疙瘩中PKC活性测定

目的　测定增生性瘢痕和瘢痕疙瘩等瘢痕组织中PKC活性变化 ,探讨PKC在瘢痕形成中的作用。方法　利用PKC活化后催化底物多肽磷酸化 ,然后计数底物中掺入32 P的放射活性的原理 ,测定增生性瘢痕、瘢痕疙瘩、成熟瘢痕和正常皮肤组织中PKC活性。结果　增生性瘢痕和瘢痕疙瘩组织中PKC的活性显著高于成熟瘢痕和正常皮肤 (P <0 .0 0 1,分别高出正常皮肤 318.30 %和 5 19.0 7% ) ,瘢痕疙瘩高于增生性瘢痕 (P <0 .0 0 1,高出 48.6 0 % )而成熟瘢痕和正常皮肤间没有差异 (P >0 .0 5 )。结论　瘢痕组织中PKC活性升高且与增生程度相关 ,提示PKC可能参与了细胞增殖和合成物质的信号转导     

增生性瘢痕和瘢痕疙瘩中PKC活性测定

目的　测定增生性瘢痕和瘢痕疙瘩等瘢痕组织中PKC活性变化,探讨PKC在瘢痕形成中的作用。方法　利用PKC活化后催化底物多肽磷酸化,然后计数底物中掺入32P的放射活性的原理,测定增生性瘢痕、瘢痕疙瘩、成熟瘢痕和正常皮肤组织中PKC活性。结果　增生性瘢痕和瘢痕疙瘩组织中PKC的活性显著高于成熟瘢痕和正常皮肤(P＜0.001,分别高出正常皮肤318.30%和519.07%),瘢痕疙瘩高于增生性瘢痕(P＜0.001,高出48.60%)而成熟瘢痕和正常皮肤间没有差异(P＞0.05)。结论　瘢痕组织中PKC活性升高且与增生程度相关,提示PKC可能参与了细胞增殖和合成物质的信号转导。     

丝裂素原激活的蛋白激酶通路与异常瘢痕形成

目的　研究丝裂素原激活的蛋白激酶 (p4 4 / 4 2MAPK)在异常瘢痕 (瘢痕疙瘩和增生性瘢痕 )中的表达和激活情况 ,探讨该信号通路在瘢痕形成中的作用。方法　用免疫印迹法 (Westernblot ting)和免疫组织化学法 ,分别检测异常瘢痕和正常皮肤的组织和成纤维细胞中 p4 4 / 4 2MAPK和磷酸化p4 4 / 4 2MAPK ,定量分析两者在各组中表达的差异。 结果　组织及其成纤维细胞中 p4 4 / 4 2MAPK含量在异常瘢痕与正常皮肤差异无显著性 ,而磷酸化 p4 4 / 4 2MAPK含量 ,以及磷酸化 p4 4 / 4 2MAPK与p4 4 /4 2MAPK之比 (ratio)明显高于正常皮肤。瘢痕疙瘩和增生性瘢痕相比 ,成纤维细胞中磷酸化 p4 4 /4 2MAPK含量在瘢痕疙瘩明显高于增生性瘢痕。结论　p4 4 / 4 2MAPK信号通路的活化在异常瘢痕形成中起作用。     

periostin在过度增生性瘢痕的表达及其与TGF-β1和受体的相关性

目的检测periostin在过度增生性瘢痕中的表达，研究其与TGF-β1和受体的相关性，探讨periostin与瘢痕过度增生的关系。方法采用RT-PCR法检测瘢痕疙瘩、增生性瘢痕、正常皮肤组织中periostin、TGF-β1，及其受体Ⅰ、Ⅱ的mRNA表达，Western blot法检测periostin的蛋白表达。结果在基因水平，periostin在瘢痕疙瘩的表达高于正常皮肤，TGF-β1在瘢痕疙瘩的表达高于增生性瘢痕和正常皮肤，TGF-βRⅠ在瘢痕疙瘩的表达高于增生性瘢痕和正常皮肤，上述差异有统计学意义（P〈0．01）；TGF-βRⅡ的表达在3组间差异无统计学意义。在蛋白水平，periostin在瘢痕疙瘩和增生性瘢痕的表达均高于正常皮肤（P〈0．05）。periostin和TGF-β1的表达呈正相关（P〈0．01）。结论periostin在瘢痕疙瘩组织中表达增高，是瘢痕相关基因；其在瘢痕疙瘩形成中可能发挥重要作用，该作用与TGF-β1密切相关。     

On the [4-14C]Progesterone Metabolism of Keloid and Hypertrophic Scar: A Preliminary Report

Tissue specimens from keloids (K) and hypertrophic scars (H), as well as from the healthy skin in their vicinity (KS resp. HS) were incubated in a medium containing [4-¹⁴C]progesterone. The metabolites were isolated and verified with thin layer chromatography. All investigated tissue types produced as metabolites of progesterone 5α-pregnane-3,20-dione, 5α-pregnane-3α, 20α-diol, as well as probably 3α/β-hydroxy-5-pregnan-20 one. The diffusion of progesterone from the medium into the tissue was most effective in K, in sharp contrast to H. The ability of the tissue to take up progesterone from the medium was nearly double in HS as compared with KS. HS seems to metabolize progesterone nearly with the same effectivity as K, and those both twice as much as KS. There were also marked differencies in the division of metabolites between the tissue and the medium.     

Panax Notoginseng Saponins suppresses TRPM7 via the PI3K/AKT pathway to inhibit hypertrophic scar formation in vitro

BackgroundHypertrophic scar (HS) formation, a type of dermal fibroproliferative condition, is a frequent complication in wound healing resulting from burns, severe trauma, and surgical procedures. The effects of Panax Notoginseng Saponins (PNS) on the HS formation remain relatively under-explored. Hence, this study was intended to interrogate anti-apoptosis and anti-fibrosis effects of PNS on the hypertrophic scar fibroblasts (HSFs) during HS formation and assess the involvement of TRPM7 and PI3K/AKT signaling pathway.MethodsUsing MTT and CCK-8 assays, we evaluated cell cytotoxicity and cell viability. Collagen I/III (col 1/3) and α-SMA expression levels were assessed through immunofluorescence and western blot, and cell migration, cell apoptosis and cell cycle were examined with applications of wound healing, TUNEL staining and flow cytometry. TRPM7, PI3K/AKT, TGF-β1 and related-proteins were quantified using RT-qPCR and western blot.ResultsPNS administration could suppress TRPM7 expression and the viability of HSFs in a dose-dependent manner. Moreover, PNS could restrain the HS formation and ECM deposition by decreasing col 1/3 and α-SMA synthesis, suppressing cell migration, and boosting apoptosis and G1 arrest. Notably, this study revealed that PNS inhibited PI3K/AKT activation in HSFs. Besides, knockdown of TRPM7 enhanced therapeutic effects of PNS on HSFs, but overexpression markedly reversed above mentioned effects of PNS on HSFs.ConclusionThis study suggested that PNS hampered scar formation might via inhibiting ECM and stimulating cell apoptosis by modulating the PI3K/AKT signaling. Overall, these findings in the present study could support the use of PNS for preventing HS formation, and TRPM7 may be a novel molecular target for treating HS.     

肌成纤维细胞在病理性瘢痕形成中的机制

目的 探讨肌成纤维细胞在病理性瘢痕形成机制中的作用。方法 对1998年～2000年门诊或住院的13例增生性瘢痕，14例瘢痕疙瘩及7例成熟瘢痕患者的相应组织，应用光镜、电镜及免疫组织化学染色，进行观察、检测。结果 增生性瘢痕的超微结构中均可见典型的肌成纤维细胞；免疫组织化学染色可见有不同程度表达的肌成纤维细胞。瘢痕疙瘩及成熟瘢痕的超微结构和免疫组织化学结果均未见肌成纤维细胞。结论 肌成纤维细胞的生物学行为可能与增生性瘢痕的形成及瘢痕畸形有关，并可用于增生性瘢痕与瘢痕疙瘩的鉴别。     

Prevalence and clinical significance of Küpffer cell hyperplasia with hemophagocytosis in liver biopsies

Hemophagocytic syndrome (HS) is a rare life-threatening condition due to uncontrolled macrophagic activation. Liver involvement is constant in HS, characterized by Küpffer cell hyperplasia with hemophagocytosis. Conversely, the specificity, frequency, and clinical significance of this histologic lesion remain poorly investigated. We aimed to evaluate the prevalence of this elementary lesion in liver biopsies (LB) to attempt to identify its clinical significance and to investigate its potential association with perforin expression deficiency. Küpffer cell hyperplasia with hemophagocytosis has been systematically searched for in consecutive LBs in a 6-year period. In positive cases, clinical, biological, and outcome characteristics have been retrospectively recorded. The ratio of perforin to CD3(+) lymphocytes was assessed on immunostained LB sections. This histologic lesion was detected in LB of 69 of 5194 patients (1.3%). It was not associated with hepatotropic viral infection, alcohol-related chronic liver disease, or autoimmune chronic liver disease. Although only 36% of patients with this histologic lesion had a complete HS (association of fever, splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia, and/or hypofibrinogenemia), almost all patients had similar underlying diseases (human immunodeficiency virus infection, malignant hemopathy, and autoimmune disease) and/or acute ongoing infections (tuberculosis, cytomegalovirus, and Epstein-Barr virus). A decrease of the perforin to CD3(+) lymphocytes ratio was specifically associated with this lesion. Küpffer cell hyperplasia with hemophagocytosis in LB is a rare finding; although it does not necessarily denote a complete HS, it is associated with the same underlying disease and/or infection, with a decrease in intrahepatic perforin-positive lymphocytes.