银屑病皮损中Survivin、VEGF和Ang—2的表达

目的：检测存活素（Survivin）、血管内皮生长因子（VEGF）及血管生成素-2（Ang-2）等因子在寻常型银屑病（PV）皮损中的表达。方法：用免疫组化方法检测30例PV皮损及30例正常皮肤组织中Survivin、VEGF及Ang-2的表达。结果：PV皮损中Survivin、VEGF及Ang-2的表达明显强于正常皮肤组织。Survivin，VEGF和Ang-2之间的表达呈正相关。结论：Survivin、VEGF及Ang-2共同参与了银屑病新生血管的生成过程。     

miR-203及其下游靶基因p63、生存素在银屑病皮损中的表达北大核心CSCD

目的 检测寻常性银屑病皮损中miR-203及其下游靶基因p63、生存素的表达水平.方法 实时PCR法检测30例寻常性银屑病患者皮损及30例健康对照皮肤中miR-203、p63、生存素mRNA的表达水平,miR-203以U6为内参照,p63和生存素以GAPDH为内参照;Western印迹法检测靶基因p63、生存素蛋白表达水平,两组间比较采用t检验,寻常性银屑病皮损中miR-203与生存素、p63表达的相关性采用Pearson相关分析.结果 与健康对照皮肤相比,寻常性银屑病皮损中miR-203 mRNA表达量为对照组的（0.41±0.11）倍,表达明显下调（t=3.16,P＜0.05）;其靶基因p63、生存素mRNA表达量分别为对照组的（4.79±0.63）和（3.43±0.46）倍,表达水平明显上调（t值分别为4.72、4.35,均P＜0.05）;靶基因p63、生存素蛋白表达量分别为对照组的（2.40±0.23）,（3.49±0.14）倍,表达水平也明显上调（t值分别为3.87、4.36,均P＜0.05）.寻常性银屑病皮损中miR-203mRNA与生存素mRNA呈负相关（r=-0.36,P＜0.05）,与p63 mRNA呈负相关（r=-0.43,P＜0.05）.结论 miR-203及其下游靶基因p63、生存素可能参与了银屑病的发病过程.     

Klf4在银屑病和湿疹患者皮损中的表达

目的：检测Klf4在银屑病及湿疹皮损中的表达。方法：采用免疫组化技术检测Klf4在16例银屑病患者皮损、16例湿疹皮损及16例正常皮肤中的表达。结果：银屑病皮损Klf4阳性细胞数为（346.56±24.91）高于正常皮肤的（235.12±20.32）,(P<0.05),湿疹皮损为（75.94±15.61）,低于正常皮肤(P<0.05)。结论：湿疹患者的Klf4表达下调而在银屑病患者中上调,KIf4在不同疾病中可能发挥不同的生物学作用。     

大麻素2型受体在寻常性银屑病皮损组织中的表达

目的 探讨大麻素2型受体在寻常性银屑病皮损组织中的表达及其意义。 方法 实时荧光定量聚合酶链反应（RT-PCR）、免疫组化技术检测20例寻常性银屑病患者皮损组织及皮损周围组织、10例非银屑病患者的正常皮肤组织中大麻素2型受体在mRNA和蛋白不同水平的表达情况。 结果 寻常性银屑病皮损组织、皮损周围组织及正常皮肤中均有大麻素2型受体mRNA表达,寻常性银屑病组表达明显高于皮损周围组及正常对照组（P < 0.05）;三组皮损组织均有大麻素2型受体蛋白表达,且寻常性银屑病组表达明显高于皮损周围组、正常对照组,差异有统计学意义（P < 0.05）。 结论 寻常性银屑病皮损组织中大麻素2型受体在基因及蛋白水平表达均升高,提示大麻素2型受体可能与寻常性银屑病的发生发展有关联。     

寻常性银屑病中P27的表达及意义

目的检测P27在银屑病皮损中的表达，探讨其在银屑病发病中的意义。方法 用免疫组化（SP法）方法检测细胞周期素依赖性蛋白激酶抑制剂（P27）在银屑病皮损及正常皮肤中的表达水平。结果 在寻常性银屑病皮损中，P27表达水平低于正常对照组，差异有显著性（P〈0．001）。结论 银屑病的发生可能与P27下调有关。     

Ang-1,2和Caspa3,5在银屑病皮损中的表达

目的：检测血管生成素1,2（Ang-1,2）和半胱氨酸蛋白酶3,5（Caspa3,5）在银屑病皮损中的表达.方法：应用免疫组化方法检测Ang-1,2、Caspa3,5在40例银屑病患者皮损及20名正常人皮肤中的表达.结果：Ang-1,2和Caspa3,5在银屑病皮损的阳性表达率分别为55.0%、75.0%、87.5%和67.5%;Ang-2表达的阳性率明显高于Ang-1,并与Caspa 3,5的表达呈正相关.结论：Ang 1,2和Caspa 3,5的高表达可能与银屑病的发病有关;Caspa 3,5可能与Ang-2具有协同作用.     

浆细胞样树突状细胞和TLR9及其mRNA在银屑病患者皮损中的表达

目的：探讨浆细胞样树突状细胞（Plasmacytoid dendritic cells,PDCs）和toll样受体9（TLR9）在银屑病发病中的表达状态。方法：采用免疫组织化学SP法和逆转录-聚合酶链反应（RT-PCR）方法检测了22例银屑病患者皮肤损害中PDCs和TLR9及其mRNA的表达。15例整形外科患者的皮肤作为正常对照。结果：免疫组化结果显示银屑病组皮损中PDCs、TLR9的表达明显增多,而在正常对照组没有表达;RT-PCR检测显示银屑病皮损中TLR9mRNA的表达明显高于正常对照组（P〈0.01）。结论：银屑病患者皮损中有PDCs浸润,TLR9及其mRNA的表达水平上调,可能与银屑病的发病相关。     

甘露糖结合凝集素在寻常性银屑病皮损中的表达

目的 检测甘露糖结合凝集素（MBL）在寻常性银屑病患者皮损中的表达,初步探讨皮肤中MBL蛋白与银屑病发病的关系。 方法 采用免疫组化法和Western印迹检测30例进行期寻常性银屑病患者皮损、非皮损区皮肤（皮损周围外观正常皮肤）及30例健康人对照皮肤中MBL的表达。采用SPSS13.0统计软件进行数据分析,组间资料比较采用t检验。 结果 免疫组化检测显示,银屑病皮损区MBL呈现阳性表达（相对表达量为0.636 7 ± 0.515 1）,非皮损区及健康对照皮肤中MBL表达弱或几乎无表达（分别为0.416 3 ± 0.160 1和0.381 6 ± 0.310 9）,银屑病皮损区较非皮损区和健康对照皮肤显著升高（t值分别为2.24和2.32,均P < 0.05）,非皮损区与健康对照皮肤MBL表达水平间比较差异无统计学意义（t = 1.51,P > 0.05）。Western印迹检测结果显示,银屑病皮损区、非皮损区及健康对照皮肤中均有MBL蛋白表达,相对表达量分别为0.273 1 ± 0.129 4、0.186 3 ± 0.193 1、0.149 2 ± 0.268 7,银屑病皮损区较非皮损区及健康对照皮肤显著增高（t值分别为2.05和2.28,均P < 0.05）,非皮损区与健康对照皮肤表达差异无统计学意义（P ＞ 0.05）。 结论 银屑病患者皮损区MBL蛋白高表达,可能与银屑病的发病存在一定关系。     

银屑病皮损VDR表达水平的研究

为了解维生素D受体（VDR）在银屑病皮损中的表达情况,采用RT－PCR方法检测了10例寻求型银屑病患者皮损VDR mRNA表达水平,并与正常人皮肤做对照。结果显示：寻常型银屑病患者皮损VDR mRNA水平明显低于 正常人皮肤（P＜0．05）,寻常型银屑病皮损VDR mRNA水平下降,可能与银屑病的发病有一定的关系。     

抗菌肽LL-37、HBD-2和HBD-3在皮肤结核皮损中的表达

目的 研究抗菌肽LL-37、人β防御素-2（HBD-2）、HBD-3在寻常狼疮和疣状皮肤结核皮损中的表达,探讨皮肤结核的发病机制。方法　免疫组化方法检测LL-37、HBD-2、HBD-3在18例寻常狼疮和疣状皮肤结核患者皮损、15例银屑病患者皮损以及10例健康人皮肤石蜡切片中的表达。SPSS13.0统计软件进行数据分析,组间行t检验。结果　LL-37、HBD-2在皮肤结核皮损中主要表达于表皮中上层、附属器及血管壁,与正常皮肤比较为高表达（t = 2.632,2.399,P值均 ＜ 0.05）,且与银屑病的表达模式类似。HBD-3在皮肤结核皮损中未见表达,而在银屑病皮损及正常皮肤中均可见表达。结论　抗菌肽LL-37和HBD-2可能参与皮肤结核的免疫反应过程,而HBD-3在皮肤结核的表达缺失可能与其发病密切相关。     

Effect of narrow band ultraviolet B on survivin in psoriatic skin lesions

Background: Suppression of apoptosis is responsible for epidermal thickness in psoriasis. Survivin is an anti-apoptotic protein that can be modulated by ultraviolet B (UVB). Aim: Our aim was to investigate the role of survivin in psoriasis and to evaluate the effect of narrow band (NB)-UVB on the survivin levels in psoriatic lesions. Methods: This study included 20 psoriatic patients and 20 healthy controls. Patients were treated with 24 sessions of NB-UVB. Skin biopsies were taken from the affected skin of each patient before and after treatment, and from the controls, to examine survivin levels by ELISA. Results: Survivin was significantly upregulated in psoriasis compared to controls (p<0.001). We found significant positive correlations between survivin levels before therapy and the extent of body involvement (r=0.675, p=0.002), as well as the PASI score (r=0.67, p=0.001). A significant decrease in survivin levels was observed post treatment compared to baseline levels (p<0.001). Conclusion: We found increased survivin levels in psoriasis and a significant reduction following NB-UVB induced clinical improvement of psoriasis.     

Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy

BACKGROUND: Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. OBJECTIVES: To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. METHODS: Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. RESULTS: Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P < 0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P < 0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P < 0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P < 0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P < 0.05) and BSA scores (r = 0.528, P < 0.024). PASI strongly correlated with BSA (r = 0.949, P < 0.0001) and DAS28 (r = 0.717, P < 0.002) scores. CONCLUSIONS: Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.     

Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias

The dysregulation of apoptosis occurs in many cutaneous disease states. Several apoptosis inhibitors have been shown elevated in neoplasms and in some inflammatory conditions, but their relation to proliferative and apoptotic states has not been defined. We examined the expression of the apoptosis inhibitor survivin in a panel of keratinocytic neoplasms and hyperproliferative skin lesions using both immunohistochemistry and a newly developed in situ hybridization technique. Proliferation and apoptotic indices were also assessed by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL, respectively. We found the highest rate of proliferation in verrucae and psoriasis followed by actinic keratosis, squamous and basal cell carcinoma, lichen simplex chronicus, and seborrheic keratosis; all were significantly (P < 0.05) higher than normal skin. Apoptotic rate was increased in squamous (P = 0.05) and basal cell carcinoma (P = 0.03), but not significantly different from normal skin in the other lesions tested. Survivin expression was seen in most neoplasms and hyperproliferative lesions, but not normal skin. Survivin expression was often restricted to the upper third of the epidermis in psoriasis and lichen simplex chronicus, whereas all the other lesions stained diffusely. Survivin expression appears to be a consistent feature of keratinocytic neoplasms and hyperproliferative lesions and may contribute to the formation of epidermal hyperplasia seen in all of these disease states.     

miR-320及下游靶基因survivin在银屑病皮损中的表达

目的检测寻常性银屑病皮损中miR-320及其下游靶基因survivin mRNA的表达水平。方法采用实时定量聚合酶链反应(RT-PCR)检测40例寻常性银屑病患者皮损及40名健康对照皮肤中miR-320、survivin mRNA的表达水平,运用双荧光素酶报告实验验证survivin是miR-320的靶基因。miR-320和survivin表达水平两组间比较采用t检验,寻常性银屑病皮损中miR-320与survivin表达的相关性采用Pearson相关分析。结果与健康对照皮肤相比,寻常性银屑病皮损中miR-320表达量为对照组的(0.561±0.11)倍,表达明显下调(t=3.06,P0.05);survivin mRNA表达量为对照组的(2.034±0.26)倍,表达水平明显上调(t=3.35,P0.05);双荧光素酶报告实验结果提示survivin是miR-320的靶基因,寻常性银屑病皮损中miR-320与survivin mRNA呈负相关(r2=0.634,P0.05)。结论 miR-320可能通过调控其下游靶基因survivin的异常表达参与寻常性银屑病皮损的形成过程。     

寻常性银屑病皮损中Survivin,Bcl-2,Caspase-3的检测及相关性分析

目的探讨Survivin、Bcl-2、Caspase-3在寻常性银屑病角质形成细胞凋亡中的可能作用。方法选择20例正常皮肤为对照组,60例寻常性银屑病患者取皮损标本,免疫组化方法对两组表皮中Survivin,Bcl-2,Caspase-3进行检测并做统计学分析,并检验Survivin与Bcl-2,Caspase-3的相关性。结果寻常性银屑病皮损中,Survivin及Caspase-3阳性细胞数明显高于正常皮肤,且进行期高于静止期(P<0.01),Bcl-2阳性细胞数明显低于正常皮肤(P<0.01),进行期与静止期无差异(P>0.05);寻常性银屑病皮损中,Survivin与Caspase-3呈正相关(P<0.01),与Bcl-2无相关性(P>0.05)。结论Sur-vivin,Bcl-2,Caspase-3在寻常性银屑病的角质形成细胞凋亡中可能起着重要作用。它们之间可能相互作用,维持寻常性银屑病表皮的良性增生状态。     

Proliferation, apoptosis, and survivin expression in a spectrum of melanocytic nevi

BACKGROUND: Apoptosis is important for maintenance of tissue homeostasis and often dysregulated in cutaneous neoplasms. The apoptosis inhibitor survivin is expressed in melanoma and non-melanoma skin cancers and benign keratinocytic lesions. Its expression has not been studied in melanocytic nevi. OBJECTIVE: We determined the expression pattern of survivin in benign melanocytic nevi in comparison to markers of proliferation and apoptosis. METHODS: Six cases of each of the following melanocytic nevi were retrieved from a dermatopathology archive: compound dysplastic nevus, intradermal nevus, compound nevus, neurotized intradermal nevus, and Spitz nevus. Survivin expression was evaluated by in situ hybridization. Apoptotic and proliferation indices were calculated by counting immunoreactive cells in terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and proliferating cell nuclear antigen immunostained sections, respectively. RESULTS: All nevi, regardless of histologic type, expressed survivin. Compound melanocytic lesions expressed survivin in both epidermal and dermal compartments. The apoptotic rate was low for dysplastic, compound, and Spitz nevi, and apoptotic cells were not identified in any neurotized nevus. The proliferative index was highest for Spitz nevi, while all other nevi demonstrated rare positive cells. CONCLUSIONS: Survivin is consistently expressed in benign melanocytic lesions, while apoptotic cells are rarely identified, suggesting the dysregulation of apoptotic pathways with the accumulation of cells in these neoplasms.