光线性角化病和鳞状细胞癌表皮生长因子受体与MAPK信号通路的研究

目的 探讨磷酸化ERK1/2、JNK和p38MAPK与其上游因子表皮生长因子受体（EGFR）及下游转录因子Elk-1在光线性角化病（AK）和皮肤鳞状细胞癌（SCC）中的表达。 方法 收集确诊为AK和高、中、低分化SCC患者各30例的病变组织,同时收集30例非癌患者正常皮肤组织作为正常对照组。采用免疫组化及Western印迹法分别检测p-EGFR、p-ERK1/2、p-JNK、p-p38MAPK及p-Elk-1蛋白在AK和不同分化程度SCC中的表达情况。 结果 p-EGFR在SCC组中的表达高于AK组及正常对照组（P < 0.05）,AK组与正常对照组表达差异无统计学意义;p-ERK1/2、p-JNK、p-p38MAPK及p-Elk-1在SCC的表达均高于AK组及正常对照组（P < 0.05）,且在AK中的表达又均高于正常对照组（P < 0.05）。除p-EGFR和p-Elk-1在高分化和中分化SCC中的表达差异无统计学意义,p-ERK1/2、p-JNK、p-p38MAPK随着SCC分化程度的降低,其表达逐渐增高（P < 0.05）。相关性分析显示,在SCC中p-EGFR的表达与p-ERK1/2、p-JNK、p-p38MAPK的表达强度呈正相关（r = 0.843、0.819、0.902,均P < 0.01）,且p-Elk-1的表达与p-ERK1/2、p-JNK、p-p38MAPK的表达强度亦呈正相关（r = 0.874、0.843、0.893,均P < 0.01）;在AK中p-EGFR的表达仅与p-p38MAPK的表达强度呈正相关（r =0.707,P = 0.022）。 结论 p-EGFR、p-ERK1/2、p-JNK、p-p38MAPK及p- Elk-1蛋白在皮肤SCC中的表达与其病理分级有关。磷酸化EGFR→ERK1/2、JNK、p38MAPK→Elk-1信号转导途径可能在AK和SCC的发生发展中起作用。     

热休克蛋白60在鳞状细胞癌、鲍温丘疹病、日光性角化病中的表达

目的探讨热休克蛋白60(HSP60)在皮肤鳞状细胞癌(SCC)、鲍温丘疹病(BP)、日光性角化病(AK)中的表达水平,比较HSP60在SCC、BP、AK病中阳性率的表达异同,发现其相关性及意义。方法以瘤旁正常组织为对照,采用免疫组化EnVision两步法测定HSP60在皮肤SCC、BP、AK肿瘤组织中的表达情况并与正常组对照。同时将皮肤SCC组依据分化程度分为低分化和高分化两组,并进行组间的阳性率表达对照。结果 HSP60在AK、BP、SCC肿瘤组织中的阳性率均显著高于瘤旁正常组织(P0.05);三组间两两比较结果为AK=SCC=BP(P0.05),无统计学意义。SCC低分化和高分化组间无统计学意义。结论 HSP60在AK、BP、SCC中高表达。HSP60的高表达可能与SCC、AK和BP的生物行为有关。     

HSP10在皮肤鳞状细胞癌、鲍温样丘疹病和日光性角化病中的表达

目的: 检测热休克蛋白10(HSP10)在皮肤鳞状细胞癌(SCC)、鲍温样丘疹病(BP)和日光性角化病(AK)中的表达。方法:采用免疫组化EnVision法检测HSP10在皮肤SCC、BP、AK中的表达。结果: 与其周围正常皮肤表达相比,BP组有统计学意义,AK和SCC组无统计学意义。AK与BP,AK与SCC阳性率比较有统计学意义(P0.05)。结论:HSP10在BP高表达,与BP的生物学行为可能有相关性。     

银屑病素在光线性角化病、Bowen病及皮肤鳞状细胞癌组织中的表达及意义

目的 研究银屑病素在光线性角化病、Bowen病及皮肤鳞状细胞癌(鳞癌)中的表达.方法 用免疫组化的方法检测18例正常皮肤组织、20例光线性角化病、25例Bowen病、21例高分化皮肤鳞癌及16例低分化鳞癌皮损中银屑病素的表达.结果 银屑病素在正常皮肤组织中表达阳性率为11.1％.在光线性角化病中19例银屑病素表达于角质层至棘层上1～3层,胞质着色,阳性率为95.0％.在Bowen病中22例银屑病素表达于表皮全层角质形成细胞,胞质着色,空泡状细胞包膜及胞质着色,阳性率为88％.在高分化鳞癌中20例银屑病素表达于角质层至棘层全层,角化珠及角化不良细胞着色,阳性率为95.2％;在低分化鳞癌中13例银屑病素表达于角质层至棘层上1～5层,低分化的鳞状细胞不着色,阳性率为92.3％.与正常皮肤组相比,银屑病素在光线性角化病、Bowen病、高分化鳞癌和低分化鳞癌中的表达差异均有统计学意义(P＜0.01).银屑病素在光线性角化病、Bowen病、高分化鳞癌中表达强度逐渐升高,而在低分化鳞癌中表达强度降低,但仍高于正常皮肤组织(P＜0.05).结论 银屑病素在鳞状细胞分化异常的皮肤病中表达异常.     

光化性角化病转化生长因子β1/Smads调控p53表达的研究

目的 通过光化性角化病(AK)皮肤组织块干扰模型探讨转化生长因子( TGF) β1/Smads对p53的调控作用.方法 培养人AK组织块,分为5个组,第1组对照组,第2组TGF β1培养24 h组,第3组SB431542培养24 h组,第4组TGFβ1培养48 h组,第5组SB431542培养48 h组,取材后实时PCR和Western印迹分别检测p53 mRNA和蛋白表达及Smad2磷酸化水平.结果 在TGFβ1培养24 h后,与对照相比,p53 mRNA表达增加(13.4968±0.9903,P＜ 0.05),Smad2磷酸化增多(0.700±0.023,P＜0.05);培养48 h后,p53 mRNA为13.3882±1.6772,蛋白为1.009±0.001,均增加(P＜0.05),Smad2磷酸化增多(0.646±0.120,P＜0.05);TGFβ1培养24 h和48 h相比,p53蛋白由0.634±0.040增加至1.009±0.001(P＜0.05);在SB431542培养24 h后,与对照相比Smad2磷酸化变化不明显,当SB431542培养48 h后,与对照相比Smad2磷酸化水平明显减少(0.116±0.003,P＜0.05),其余没有明显变化.结论 人AK皮肤组织块培养可作为一种信号通路的干扰模型,TGFβ1在AK中可通过Smads通路调控p53表达.     

Raptor、Rictor和磷酸化Akt在日光性角化病、Bowen病及鳞状细胞癌中的表达

目的:检测Raptor、Rictor和磷酸化Akt(p-Akt)在日光性角化病、Bowen病和鳞状细胞癌中的表达。方法:采用免疫组化法检测Raptor、Rictor及p-Akt(Ser473)在20例正常皮肤、20例日光性角化病、20例Bowen病及40例鳞状细胞癌中的表达。结果:Raptor在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为87.50%、70.00%和60.00%,均高于正常皮肤的25.00%(均P0.05);其中低分化鳞状细胞癌中Raptor的阳性表达率为100%,高于高分化鳞状细胞癌的阳性表达率75%(P0.05)。Rictor在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为80.00%、70.00%及55.00%,均高于正常皮肤阳性表达率的20%(均P0.05);p-Akt(Ser473)在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为77.50%、65.00%及50.00%,而正常皮肤阳性表达率为0。鳞状细胞癌、Bowen病和日光性角化病中Rictor的阳性表达水平和p-Akt(Ser473)的阳性表达水平均呈正相关(均P0.05)。结论:Raptor、Rictor和p-Akt(Ser473)的高表达可能与日光性角化病、Bowen病和鳞状细胞癌的发生发展有关。     

紧密连接蛋白Claudin-1、7在日光性角化病和皮肤鳞状细胞癌中的表达

目的：检测紧密连接蛋白Claudin-1、7在日光性角化病(AK)和皮肤鳞状细胞癌（SCC）中的表达水平。方法：收集2014年11月至2016年11月我院病理科AK和SCC组织标本各30例,选取癌旁正常皮肤组织30例作为对照组,采用免疫组化方法检测癌旁正常表皮、AK和SCC组织中Claudin-1、7蛋白的表达。结果：对照组、AK和SCC组织中Claudin-1蛋白细胞阳性率分别为100%,53.33%和13.33%,三组两两比较,差异均有统计学意义(Ps<0.05)。Claudin-7在癌旁正常表皮、AK和SCC组织中均呈阴性表达。结论：Claudin-1蛋白在癌旁正常表皮、AK和SCC组织中表达水平逐渐下降,Claudin-1蛋白表达下调可能与表皮肿瘤的恶性转化有关。     

氨基酮戊酸光动力疗法对鳞状细胞癌细胞株A431蛋白激酶D1及其磷酸化位点的影响

目的 研究氨基酮戊酸光动力疗法（ALA-PDT）对皮肤鳞状细胞癌A431细胞蛋白激酶D1（PKD1）的影响,探讨ALA-PDT诱导A431细胞凋亡的机制。方法 体外培养A431细胞,用CCK-8法检测筛选出抑制作用最强的ALA浓度和光动力照射（PDT）剂量组合。将对数期生长A431细胞随机分为不予任何干预的对照组、ALA组、PDT组及ALA-PDT组,观察4组细胞接受相应干预12、24、36、48 h后细胞增殖抑制率和增殖抑制作用最强时间点的凋亡率。反转录PCR检测ALA-PDT作用A431细胞不同时间点后各组PKD1基因mRNA的表达。Western 印迹法检测各组A431细胞中PKD1及其磷酸化位点Tyr463蛋白（pTyr463）、Ser916蛋白（pSer916）表达。结果 ALA浓度1.5 mmol/L、光照剂量2 J/cm2为最佳剂量组合。4组细胞干预12、24、36、48 h的增殖抑制率差异有统计学意义（F = 39.56,P < 0.05）。孵育24 h时：ALA-PDT组细胞增殖抑制率（46.26% ± 1.25%）高于ALA组（14.65% ± 0.33%）、PDT组（14.96% ± 0.68%）和对照组（11.98% ± 0.32%）,差异有统计学意义（均P < 0.05 ）;ALA-PDT组细胞增殖抑制率高于12 h（P < 0.05）;4组细胞凋亡率差异有统计学意义（F = 16.32,P < 0.05）,ALA-PDT组（41.92% ± 3.23%）高于对照组（4.67% ± 0.88%）、ALA组（7.02% ± 1.52%）和PDT组（8.37% ± 0.59%）,均P < 0.05。ALA-PDT作用于A431细胞后0、6、12、24、36、48 h,细胞PKD1基因mRNA的相对表达量差异有统计学意义（F = 22.24,P < 0.05）,孵育24 h mRNA相对表达量低于0、6、12 h（均P < 0.05）,与36、48 h差异无统计学意义（均P > 0.05）。4组A431细胞中pSer916表达量差异无统计学意义（F = 1.53,P > 0.05）,PKD1和pTyr463表达量差异有统计学意义（F值为10.04、8.27,均P < 0.05）,ALA-PDT组PKD1、pTyr463的表达低于对照组、ALA组、PDT组（均P < 0.05）。结论 PKD1可能参与ALA-PDT疗法诱导A431细胞凋亡的光化学反应进程,且可能是通过Tyr463位点活化促进癌变的发展。     

端粒酶在鳞状细胞癌和Bowen病组织中的表达

目的探讨端粒酶在皮肤鳞状细胞癌(SCC)及Bowen病(BD)病变组织中的表达及其临床意义。方法应用原位杂交方法检测30例皮肤SCC和30例BD病变组织中端粒酶基因hTR和hTERTmRNA的表达。结果在BD组织中hTR和hTERTmRNA呈弱表达,阳性率为23.33%和16.67%。在SCC中,hTR和hTERTmRNA的阳性率分别为86.67%和93.33%。其中Ⅰ、Ⅱ级SCC阳性率分别为82.35%和88.24%,无强阳性;Ⅲ、Ⅳ级SCC阳性率分别为92.31%和100%、强阳性表达率分别为69.23%和76.92%。SCC和BD两者比较差异有显著性(P<0.05)。SCCⅠ、Ⅱ级与Ⅲ、Ⅳ级比较差异有显著性(P<0.05)。结论端粒酶hTR和hTERTmRNA的表达增多是预测皮肤SCC的重要因素。     

E-钙黏素在鳞癌、Bowen病和脂溢性角化病中的表达

目的: 检测E-钙黏素(E-cadherin)在皮肤鳞状细胞癌(SCC)、Bowen病(BD)、脂溢性角化病(SK)中的表达.方法: 用免疫组化染色方法检测10例正常皮肤,20例SCC、20例BD、20例SK中E-钙黏素的表达.结果: E-钙黏素在SK表皮中的表达与正常表皮相似,在SCC中表达显著减弱或完全无表达,而在Bowen病表皮正常区域表达正常或下调.结论: E-钙黏素在恶性皮肤癌中表达异常,可能与表皮肿瘤的侵袭和转移有关.     

热休克蛋白10、60在皮肤鳞状细胞癌、基底细胞癌、日光性角化病中的表达

目的 探讨热休克蛋白（HSP）10、60在皮肤鳞状细胞癌（SCC）、基底细胞癌（BCC）和日光性角化病（AK）中的表达水平。方法 采用免疫组化EnVision两步法测定HSP10、60在皮肤SCC、BCC、AK中的阳性表达水平,并与正常组对照。结果 与对照组比较,HSP10组只有BCC组的阳性表达高于正常组（Z = 3.24,P < 0.01）,AK组（Z = 0.74,P > 0.05）和SCC组（Z = 0.52,P > 0.05）与对照组比较差异无统计学意义;HSP10组中AK与BCC,AK与SCC的差异有统计学意义（P < 0.05）,但SCC与BCC组间差异无统计学意义（P > 0.05）。HSP60组三组的阳性表达均高于正常组,其中AK（Z = -2.90,P < 0.01）、BCC（Z = -2.15,P < 0.05）、SCC（Z = -2.78,P < 0.01）;三组间两两比较结果为AK = SCC > BCC（P < 0.05）。结论 HSP60的高表达可能与鳞状细胞癌、日光性角化病的生物行为有关。     

SGK1在日光性角化病、基底细胞癌及鳞状细胞癌中的表达

目的：检测SGK1在日光性角化病（AK）、基底细胞癌（BCC）及鳞状细胞癌（SCC）中的表达。方法：采用免疫组化SABC法检测SGK1在25例正常皮肤(NS)、25例AK、28例BCC、28例皮肤鳞状细胞癌标本中的表达。结果：NS、AK、BCC和SCC标本中,SGK1阳性细胞率分别为（40.03±14.42）%,（36.63±14.28）%,（52.82±18.73）%和（52.58±20.13）%。BCC组和SCC组分别与NS组比较,差异均有统计学意义（Ps<0.05）。各组SGK1染色阳性细胞率>50%的标本分别为6例（24%）,3例（12%）,16例（57.14%）和14例（50%）,BCC组和SCC组分别与NS组比较,差异均有统计学意义（Ps<0.05）。结论：SGK1的高表达可能与基底细胞癌及鳞状细胞癌的发病有关。     

Cyclin A and beta-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin

BACKGROUND: Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of beta-catenin, the molecule involved in cell-cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. OBJECTIVES: To determine cyclin A and beta-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. METHODS: Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin-biotin technique using antibodies to cyclin A and beta-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC-11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for beta-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. RESULTS: Diffuse cyclin A presence was observed more frequently in BD than in AK (P < 0.0001) or SCC (P = 0.0002), and in SCC-PD compared with SCC-WD (P < 0.0001) or SCC-MD (P = 0.0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant (P < 0.0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 (P < 0.0001). Cyclin A LI was significantly lower (P < 0.05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent beta-catenin membranous staining was found in 90 cases (81.8%), more often in SCC than in AK (P = 0.03) or in AK and BD grouped together (P = 0.02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous beta-catenin staining showed 36 lesions (32.7%), more frequently SCC than AK (P = 0.003) or AK and BD grouped (P = 0.006), as well as SCC-PD compared with SCC-WD (P = 0.01) and SCC-MD (P = 0.03), whereas all KIN comparisons remained nonsignificant. Aberrant beta-catenin cellular localization demonstrated 28 lesions (25.5%), most often in the basal or peripheral parts and in the lesions with diffuse beta-catenin loss (P = 0.009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous beta-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm (P = 0.03), while all other comparisons between cyclin A or beta-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining (P = 0.001) or with aberrant cellular localization of beta-catenin (P = 0.002). CONCLUSIONS: Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced beta-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous beta-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of beta-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions (in situ, partial thickness) are grouped.     

Increased expression of an epidermal stem cell marker, cytokeratin 19, in cutaneous squamous cell carcinoma

Background Cytokeratin 19 (CK19) has been considered to be a putative marker for epidermal stem cells in the hair follicle bulge. Cumulative reports have shown that epidermal stem cells play an important role in skin carcinogenesis. However, to date there has been no report on the clinical alteration of the stem cells in squamous cell carcinoma (SCC). Objectives To investigate alteration of the stem cells and proliferating cells and to assess their relationship and potential contribution to SCC. Methods Thirty paraffin‐embedded neoplastic skin lesions, consisting of 10 cases each of actinic keratosis (AK), Bowen disease (BD) and SCC, were examined immunohistologically for CK19 and Ki‐67. Results Positive reactivity for CK19 was seen in 30% of AK, 50% of BD and 80% of SCC lesions. There was significantly higher expression levels of CK19 in SCC than in AK and BD (P < 0·05). In addition, BD lesions harboured a significantly higher number of CK19‐positive cells than did AK lesions (P < 0·05). There were significant differences in Ki‐67 labelling indices between AK and BD and between AK and SCC (P < 0·001), but not between BD and SCC (P > 0·05). Furthermore, a serial section comparison study showed that there was a minor population of cells co‐expressing CK19 and Ki‐67 in a subset of the tumour cells of SCC samples. The percentage of CK19+ cells significantly correlated with that of Ki67+ cells in all examined neoplastic skin lesions. Conclusions These results suggest that CK19 expression may be associated with the retention of stem cell characteristics or a state that is uncommitted to terminal squamous differentiation.     

Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors

Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various cancers, including experimentally promoted tumors, gastrointestinal cancers, breast tumors and skin tumors. The mechanism that controls COX-2 expression is not yet clear. Currently, it is reported that COX-2 expression is frequently associated with mutated p53 genes. The goal of this study was to evaluate the expression patterns of COX-2 and p53 in several skin tumors and their correlation. An immunohistochemical method was used to investigate the expression of COX-2 and p53 proteins on formalin-fixed, paraffin-embedded tissue specimens of squamous cell carcinomas (SCC), basal cell carcinomas (BCC), Bowen's disease (BD), actinic keratosis (AK) and porokeratosis. The expression of COX-2 increased in 50% (5/10) of SCC, 80% (8/10) of BCC, 40% (4/10) of BD, 50% (5/10) of AK, and 20% (2/10) of porokeratosis cases. The expression of p53 increased in 90% (9/10) of SCC, 70% (7/10) of BCC, 70% (7/10) of BD, 50% (5/10) of AK, and 40% (4/10) of porokeratosis cases. COX-2 positivity rates of the p53-positive skin tumors were 56%, 100%, 57%, 80% and 25% in SCC, BCC, BD, AK and porokeratosis, respectively. However, the correlation between p53 and COX-2 expression in skin tumors was not statistically significant ( P  > 0.05). Our results indicate that skin COX-2 and p53 may play roles in skin tumors, but that there is no apparent correlation between the two markers.     

NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP

BackgroundNUAK2 is a critical gene that participates in the carcinogenesis of various types of cancers including melanomas. However, the expression patterns of NUAK2 in normal skin and in various types of skin tumors have not been fully elucidated to date.ObjectivesTo elucidate the distribution and localization of NUAK2 expression in normal skin, and characterize the expression patterns of NUAK2 and YAP in various types of skin tumors.MethodsIn this study, we characterized the expression of NUAK2 in tissues by developing a novel NUAK2-specific monoclonal antibody and using that to determine NUAK2 expression patterns in normal skin and in 155 cases of various types of skin tumors, including extramammary Paget’s disease (EMPD), squamous cell carcinoma (SCC), Bowen’s disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC) and angiosarcoma (AS). Further, we analyzed the expression patterns of YAP and p-Akt in those tumors.ResultsOur analyses revealed that NUAK2 is expressed at high frequencies in EMPD, SCC, BD, AK, BCC and AS. The expression of p-Akt was positively correlated with tumor size in EMPD (P = 0.001). Importantly, the expression of NUAK2 was significantly correlated with YAP in SCC (P = 0.012) and in BD (P = 0.009).ConclusionsOur results suggest that the YAP-NUAK2 axis has critical importance in the tumorigenesis of SCC and BD, and that therapeutic modalities targeting the YAP-NUAK2 axis may be an effective approach against skin tumors including SCC and BD.     

强功率UVA1对兔耳增生性瘢痕模型影响的机制研究

目的 探讨不同剂量UVA1对全层皮肤缺损诱导的兔耳增生性瘢痕模型的影响的可能机制。方法 24只新西兰白兔双耳腹面手术切除2 cm × 5 cm全层皮肤至筋膜建立兔耳增生性瘢痕模型后,随机分成4组,每组6只,将每只兔左耳分别于伤后即刻（U0）、1个月（U1）、2个月（U2）、3个月（U3）开始强功率UVA1照射,右耳为非照射组;各照射组分为两个剂量组［60 J/cm2（M）,110 J/cm2（H）］,分别在照射前后进行MMP-1、TIMP-1、TGF-β1、PCNA和α-SMA的免疫组织化学染色和透射电镜检查。结果 与照射前比较,中高剂量组照射后瘢痕处MMP-1表达：U1组分别为10.43 ± 1.61、11.16 ± 1.57;U2组分别为8.63 ± 2.61、7.33 ± 1.58;U3组分别为5.74 ± 1.43、3.11 ± 0.27;均显著增加（P < 0.05）。TGF-β1表达：U1组分别为12.51 ± 4.13、12.02 ± 5.02;U2组分别为18.74 ± 6.42、19.69 ± 4.52;U3组分别为20.51 ± 1.78、29.45 ± 6.55。PCNA表达：U1组分别为2.67 ± 0.44、2.04 ± 0.65;U2组分别为4.50 ± 0.97、5.82 ± 0.68;U3组分别为7.45 ± 1.47、8.16 ± 1.07;均显著降低（P < 0.05）。只有高剂量组显著降低TIMP-1表达,U1组为12.74 ± 4.58,U2组为15.17 ± 3.26,U3组为20.72 ± 3.31（P < 0.05）。只有U1H、U1M、U2H组α-SMA表达（1.33 ± 0.34、2.04 ± 0.20、3.60 ± 1.75）显著降低（P < 0.05）。U0组：与对照组比较,高剂量组MMP-1表达（2.25 ± 0.38）显著降低（P < 0.05）,而TGF-β1表达（23.90 ± 2.92）显著增加（P < 0.05）。中、高剂量组PCNA（7.42 ± 0.65、7.59 ± 0.31）、TIMP-1（29.82 ± 1.94、33.51 ± 1.19）及α-SMA表达（6.31 ± 0.61、2.97 ± 0.56）均显著增加（P < 0.05）。透射电镜结果显示：强功率UVA1照射后胶原纤维直径变细;成纤维细胞胞质变少,细胞器欠发达,多数为静止的纤维细胞。结论 UVA1对瘢痕的作用可能与其抑制TGF-β1、TIMP-1、PCNA和α-SMA的表达,同时促进MMP-1的表达,从而促进基质蛋白降解及抑制成纤维细胞和肌成纤维细胞的增值活性有关。如果UVA1过早干预,则会出现相反的结果。