用组织芯片技术研究光暴露皮肤与非光暴露皮肤的细胞凋亡

目的：应用皮肤组织芯片方法检测光暴露部位和非光暴露部位皮肤细胞凋亡情况。方法：组织芯片按文献方法制备，用免疫组化链霉亲和素-生物素法(Streptavidin-Peroxidase SP)观测P153、bcl-2蛋白在18例光暴露与非光暴露皮肤组织的表达。结果：在18例光暴露皮肤中P153表达均为阳性，阳性表达位于基底细胞及棘细胞全层，呈散在分布。随年龄增加相应增加，与性别无关。11例非光暴露皮肤中，仅4例弱阳性，阳性表达位于棘层上方只见于孤立棘细胞，其它部位未发现阳性表达。bcl-2在光暴露部位与非光暴露部位均为阴性。结论：光暴露部位凋亡诱导因子P53均上调，这一特征性表达进一步揭示细胞凋亡参与紫外线诱导皮肤老化和肿瘤形成。     

非光暴露皮肤经窄谱中波紫外线照射前后MMP-1的表达

目的探讨非光暴露皮肤经窄谱中波紫外线B(NB-UVB)照射前后基质金属蛋白酶-1(MMP-1)的表达及意义。方法观察志愿者照光前后的非光暴露皮肤的光老化表现;免疫组化检测其照光前后皮肤MMP-1的表达;用ELISA方法检测不同剂量NB-UVB照射后人成纤维细胞MMP-1的表达。结果所有病例均出现皮肤光老化表现。28例志愿者中MMP-1的表达光照前5例(17.90%)阳性,光照后9例(32.10%)阳性(P<0.05)。不同剂量的NB-UVB(0,10,20,30,50,60,80,120mJ/cm2)照射后,成纤维细胞的MMP-1的表达在20mJ/cm2时明显增高,有统计学意义(P<0.05),并呈剂量依赖方式增高。结论NB-UVB照射对MMP-1的表达起促进作用。推测NB-UVB促进MMP-1的表达,加快皮肤胶原蛋白的分解,加速皮肤老化。     

光暴露及光防护措施与系统性红斑狼疮临床病情相关性研究

目的 探讨系统性红斑狼疮患者的日光暴露时间及光防护措施与其病情的相关性.方法 询问107例系统性红斑狼疮患者日光暴露及光防护措施的态度及行为,并对患者的临床表现、实验室检查指标及治疗予以评估.结果 48例(44.86%)患者每日光暴露<1h,59例(55.14%)患者每日光暴露≥1h.24例(22.43%)患者春、夏两季外出时采取光防护措施.每日光暴露<1h组患者光敏感性、关节痛、脱发、疾病活动、抗dsDNA抗体、C3<800mg/L、C4<180mg/L及CH50<90kU/L的发生率明显低于每日光暴露≥1h组的患者(P<0.05).肾脏受累的发生率两组差异无统计学意义,但前者肾受累的严重程度(尿蛋白>+++)明显低于后者(P<0.01).每日光暴露<1h组治疗使用硫酸羟氯喹片、中高剂量醋酸泼尼松片及联合环磷酰胺冲击治疗的频率均低于每日光暴露≥1h组.治疗后面部蝶形红斑、发热、关节痛及抗核抗体的改善,两组差异无统计学意义,但尿蛋白转阴天数前者明显短于后者(P<0.05).结论 系统性红斑狼疮患者应减少过度日光暴露,加强光防护措施.     

应用组织芯片技术观察曝光皮肤中Ki67蛋白的表达

目的：比较曝光皮肤与非曝光部位皮肤组织的Ki67的表达情况。方法：使用组织芯片技术用免疫组化链霉亲和素-生物素法（Streptavidin Perroxidase,SP）进行检测。结果：在33例曝光皮肤中阳性16例（48.5%）,阴性17例（51.5%）,在18例非曝光皮肤中阳性17例（94.4%）（χ^2=86.5,P〈0.05）。同组中随着年龄增加,Ki67蛋白表达有波动;皱纹重较皱纹轻表达减少。银屑病5例,扁平苔藓5例均为强阳性,湿疹5例为中等强度阳性,脂溢性角化病2例强阳性。曝光皮肤组织Ki67表达较非曝光部位皮肤组织的Ki67蛋白表达减少。银屑病、扁平苔藓、脂溢性角化病Ki67表达与正常皮肤进行比较有明显增强。阳性表达分布于细胞核,位于基底细胞层及表皮全层。结论：（1）日光对细胞增殖因子的表达起抑制作用。（2）增殖性皮肤病及良性肿瘤细胞增殖能力强于炎性皮肤病,炎性皮肤病细胞增殖能力较正常组织强,正常皮肤组织细胞增殖能力较光曝晒组织强。     

免疫荧光法检测cathepsins在人慢性光损伤皮肤中的表达变化

目的:用免疫荧光检测cathepsins家族的几个重要亚型在人慢性光损伤皮肤中的表达变化并探讨其意义。方法:用日光模拟紫外线照射以1倍最小红斑量(MED)照射10名受试者上臀部皮肤,5天/周,共6周,人工诱导皮肤慢性光损伤。免疫荧光法检测cathepsin B、D、K、G在人慢性光损伤皮肤中的表达变化。结果:在慢性光损伤人皮肤组织中,cathepsin B和cathepsin D表达下调,表达改变主要发生于皮肤表皮层;cathepsin K表达下调,表达改变主要发生于皮肤真皮层;cathepsin G表达上调,表达改变主要发生于皮肤真皮层。结论:cathepsins家族在人皮肤慢性光损伤皮肤表达发生改变,其可能参与皮肤表皮及真皮的慢性光损伤发生机制。     

组织蛋白酶B在光老化皮肤中的表达及意义

目的 探讨组织蛋白酶B在光老化皮肤中的表达意义。方法 6例成人曝光和非曝光皮肤标本,采用免疫组化法定位及对比组织蛋白酶B的表达。体外培养原代人皮肤成纤维细胞,甲氧沙林 ＋ UVA法体外诱导培养细胞光老化。衰老相关-β-半乳糖苷酶染色证明老化诱导成功。Western印迹技术及RT-PCR对比检测光老化成纤维细胞及正常成纤维细胞组织蛋白酶B蛋白及基因表达。结果 6例成人曝光和非曝光活体皮肤均见组织蛋白酶B阳性染色,和非曝光部位相比,曝光部位皮肤阳性染色A值降低。Western印迹结果示,成纤维细胞光老化诱导组蛋白表达较UVA诱导组、甲氧沙林孵育组及空白组明显下调。光老化成纤维细胞诱导后1周,组织蛋白酶B与内参的灰度比由28.099 ± 0.054下降为25.103 ± 0.102,诱导后3周灰度值进一步下降为17.693 ± 0.099。实时定量RT-PCR结果示,光老化细胞组织蛋白酶B mRNA表达下调为正常组的64％（P < 0.05）。结论 组织蛋白酶B在光老化皮肤及老化成纤维细胞中表达降低,且有时间依赖性,与光老化皮肤自我修复能力下降有关。     

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。     

MIC-1和uPA蛋白在皮肤鳞状细胞癌组织中的表达及与组织学分级和发病部位的关系

目的 探讨MIC-1和uPA蛋白在皮肤鳞状细胞癌中的表达及与组织学分级和发病部位的关系。方法 应用免疫组化SP法检测42例皮肤鳞状细胞癌组织及42例正常对照皮肤中MIC-1及uPA蛋白的表达,并分析其与组织学分级及发病部位的关系。结果 皮肤鳞状细胞癌组织中MIC-1(66.67%)及uPA蛋白(78.57%)阳性表达率均显著高于正常对照皮肤组织中的阳性表达率(16.67%和28.57%),差异均有统计学意义(P均<0.05);皮肤鳞状细胞癌组织中MIC-1及uPA蛋白阳性表达率均与鳞状细胞癌病理组织学分级密切相关(P均<0.05);MIC-1与uPA蛋白的表达呈正相关(P<0.05)。结论 皮肤鳞状细胞癌组织中MIC-1和uPA蛋白的表达均显著升高,其高表达可能与皮肤鳞状细胞癌发生和发展有关。     

IGFBP7在皮肤黑素瘤组织和细胞系中的表达

目的:检测胰岛素样生长因子结合蛋白7(IGFBP7)在皮肤黑素瘤组织和细胞系中的表达。方法:免疫组化法检测25例原发性皮肤黑素瘤、5例转移性皮肤黑素瘤、20例良性色素痣、10例正常皮肤组织和4株人黑素瘤细胞系中IGFBP7的表达。结果:IGFBP7在正常皮肤和良性色素痣细胞浆中的阳性表达率为85%,而在皮肤黑素瘤胞浆中的阳性表达率为16%和20%。除人黑素瘤细胞系MV3阳性表达IGFBP7外,其余细胞系均阴性表达。结论:IGFBP7在皮肤黑素瘤组织和细胞系中的低表达或功能缺失可能参与了皮肤黑素瘤的发病。     

慢性盘状红斑狼疮和亚急性皮肤型红斑狼疮的免疫组化研究——免疫病理机制的探讨

应用碱性磷酸酶和单克隆抗碱性磷酸酶方法(APAAP)对18例皮肤型红斑狼疮患者的皮肤活检标本进行了免疫组化研究。其中慢性盘状红斑狼疮(CDLE)10例(男2、女8),亚急性皮肤型红斑狼疮(SCLE)8例(男1、女7)。取材时所有病例均未接受全身治疗。对照组为4例健康人。取光暴露部位皮损和光暴露部位的正常皮肤冰冻切片,进行组化染色。结果:①在10     

Sun exposed skin disease

A wide variety of dermatoses may arise in exposed areas and are at the same time induced or exacerbated by irradiation from the sun. The spectrum may range from acute sunburn to chronic effects of sun damage, including elastosis and ultraviolet-induced skin cancer. Inflammatory ultraviolet-induced dermatoses have a confusing nomenclature and classification that often leads to difficulties in the differential diagnosis. Modern nosology differentiates primary from secondary photodermatoses. Primary photodermatoses are believed to be mainly irradiation-induced and immunologically mediated. If the pathophysiology is not clearly defined, they are also called idiopathic. In cases of a known photosensitizer, local and systemic phototoxic or photoallergic reactions can be differentiated. Secondary photodermatoses have an established pathophysiology; for example, an enzyme defect such as occurs in the porphyrias or xeroderma pigmentosum, which leads to the abnormal sun sensitivity. Finally, preexisting dermatoses may be exacerbated by irradiation from the sun, as in systemic lupus erythematosus or Darier disease.     

Multiple nonmelanoma skin cancer in an exposed Australian population

BACKGROUND: Patients with nonmelanoma skin cancer (NMSC) frequently develop multiple skin cancers. The study presents incidence rates and rates of excision of NMSC for a population living in a high-risk environment for skin cancer. METHODS: Between 1997 and 1999 a prospective population-based study collected information on all histologically confirmed NMSCs in Townsville, Australia. RESULTS: Of the 6708 patients recorded with NMSC, 38.5% had multiple lesions. Yearly age-standardized incidence rates (per 100,000 inhabitants) of basal cell carcinoma (BCC) were 1444.8 for men, 942.7 for women, and of squamous cell carcinoma (SCC) were 805.0 for men, and 423.6 for women. Compared to incidence rates, age-standardized rates of lesions of BCC were 2.1 times higher in men, 1.6 times higher in women, and of SCC were 1.8 times higher in men and 1.4 times higher in women. CONCLUSIONS: The occurrence of multiple NMSCs compromises results of short-term studies on incidence. Further discussions on the most appropriate strategies to describe the real burden of NMSC are warranted.     

Lichen ruber only in skin areas exposed to light

In a patient with lichen ruber, skin lesions appeared exclusively on sun-exposed sections of the body. This localization is atypical in Europe. In tropical and subtropical countries lichen ruber actinicus can be observed in up to 30% of the population.     

Permeability barrier function of skin exposed to ionizing radiation

OBJECTIVE: To characterize the epidermal permeability barrier function of skin during exposure to ionizing radiation. DESIGN: A prospective cohort study. SETTING: University hospital medical center. PATIENTS: Fifteen women receiving local radiation therapy (5000-6000 rad [50-60 Gy]) following breast-conserving surgery for breast cancer. MAIN OUTCOME MEASURES: Clinical symptoms and transepidermal water loss (TEWL). RESULTS: Epidermal permeability barrier function is impaired in patients who exhibit clinical signs of radiation dermatitis. The functional damage to the stratum corneum induced by ionizing radiation occurs with a delayed course, starting within a mean period of 11 days and reaching maximal values after a mean period of 27 days (range, 13-75 days). The onset of TEWL increase precedes the onset of radiation dermatitis and the maximal TEWL measurements precede the peak of skin changes. Patients with an early onset of TEWL increase show a longer duration of skin symptoms. CONCLUSIONS: Skin changes caused by radiation dermatitis are associated with an increase in TEWL. The barrier impairment is comparable to the changes observed with UV radiation exposure but exhibits an even more delayed course. Our results suggest that preservation of the epidermal permeability barrier function by topical treatment may ameliorate radiation dermatitis.