银屑病中细胞凋亡相关基因bcl-2、Fas、bax的检测

为了细胞凋亡相关基因ｂｃｌ－２、Ｆａｓ、ｂａｘ在银屑病发病中的意义,采用免疫组化ＡＢＣ法、ＳＡＢＣ法检测了这几种基因在１５例银屑病中的表达。结果发现银屑病的角质形成细胞中抑凋亡基因ｂｃｌ－２几乎不表达,促凋亡基因Ｆａｓ、ｂａｘ阳性表达。揭示促凋亡基因Ｆａｓ、ｂａｘ在银屑病中发病起重要作用,而抑凋亡基因ｂｃｌ－２作用可能不大。     

寻常性银屑病皮损中bcl—2 Fas及FasL的表达

目的 探讨银屑病表皮角质形成细胞异常增殖和分化机制。方法 采用免疫组化技术对１０例建党性银屑病皮损中ｂｃｌ－２、Ｆａｓ及ＦａｓＬ表达进行了检测。结果 在建党惺 银屑病皮损中,７例表达ｂｃｌ－２,且表达部位主要位于棘细胞层上方和角质层内角化不全细胞;１０例表达Ｆａｓ,表达部位与ｂａｌ－２相似‘浸润炎性细胞均不表达ＦａｓＬ。相关分析表明,角质形成细胞ｂｃｌ－２和Ｆａｓ表达强度呈显著性相关（ｒ＝－０．７     

在基底细胞癌和鳞状细胞癌皮损中bcl—2与Fas蛋白的表达

为了探讨细胞凋亡抑制基因ｂｃｌ－２（Ｂ－ｃｅｌｌｌｙｍｐｈｏｍａ／ｌｅｕｋｅｍｉａ２）及凋亡基因Ｆａｓ与皮肤基底细胞癌（ＢＣＣ）及鳞状细胞癌（ＳＣＣ）发生、发展的关系，对１３例ＢＣＣ及１１例ＳＣＣ皮损进行了ｂｃｌ－２蛋白和Ｆａｓ抗原的免疫组化研究。１１例ＳＣＣ中Ⅰ级６例、Ⅱ级３例、Ⅲ级２例。结果１３例ＢＣＣ肿瘤组织全层ｂｃｌ－２均染色阳性，而无任何Ｆａｓ阳性着色；１１例ＳＣＣ无１例ｂｃｌ－２染色阳性，却全部出现Ｆａｓ阳性细胞，且Ｆａｓ的表达强度与肿瘤分化程度呈正相关。该结果证明：ｂｃｌ－２表达见于ＢＣＣ，而不见于ＳＣＣ；Ｆａｓ表达则见于ＳＣＣ，而不见于ＢＣＣ。这种区别反映出两种皮肤肿瘤在发病机理上的差异     

皮肤鳞状细胞癌的细胞凋亡及某些凋亡相关基因产物的表达

目的观察皮肤鳞状细胞癌（ＳＣＣ）的细胞凋亡及ｐ５３、ｂｃｌ ２、Ｂａｘ和Ｆａｓ蛋白的表达。方法采用ＴＵＮＥＬ法和免疫组化染色。结果在２２例ＳＣＣ病变组织中,均可见到细胞凋亡,分化差、核分裂像多的ＳＣＣ中凋亡细胞较多,而分化好、核分裂像少的ＳＣＣ中则凋亡细胞少。在２７例ＳＣＣ中,１６例ｐ５３阳性表达,１４例ｂｃｌ ２阳性,１９例Ｂａｘ阳性,６例Ｆａｓ阳性。结论ＳＣＣ的发生与细胞凋亡及某些凋亡相关基因产物的异常表达有关。     

银屑病患者表皮及真皮中Bcl-X、Bcl-2、Bax表达的免疫组化研究

目的 探讨银屑病患者细胞增殖与凋亡的调节。方法 用免疫组化ＳＰ法检测银屑病皮损及非皮损中Ｂｃｌ－Ｘ、Ｂｃｌ－２、Ｂａｘ的表达情况。结果 银屑病皮损中,Ｂｃｌ－Ｘ在表皮各层、真皮炎症细胞及血管内皮的表达均较正常明显增高;Ｂａｘ在颗粒层与棘层的表达轻度增高。上述异常在非皮损中已经部分存在,且隍未完全恢复正常。而Ｂｃｌ－２表达与正常相似,局限于基底层黑素细胞,角质形成细胞未是性。结论 银屑病中角质形成细     

银屑病患者皮损中细胞凋亡情况的评价

目的 探讨细胞恨与银屑病的关系。方法 用免疫组化ＳＰ法检测银屑病皮损与非皮损中Ｂａｘ、Ｆａｓ、Ｆａｓ－１的表达,并用ＴＵＮＥＬ（末端脱氧核苷酰转移介导的ｄ－ＵＴＰ－生物素缺口本端标记）技术检测细胞凋亡情况。结果 与正常人相比,银屑病表皮角质形成细胞,真皮炎症细胞及炎症细胞及血管内皮均存在不同程度的上述蛋白的过度表达,伴细胞凋亡增多,部分在治疗后末完全恢复正常。结论 推测银屑病皮损中角质形成对细胞过     

c－myc、p53和bcl－2与银屑病角质形成细胞凋亡异常关系的研究

目的 探讨原癌基因ｃ－ｍｙｃ、抑癌基因ｐ５３和凋亡保护基因ｂｃｌ－２在银屑病角质形成细胞凋亡异常中的作用。方法 采用免疫组化和非同位素核酸原位杂交技术从蛋白和ｍＲＮＡ二个水平检测了３６份建党型银屑病皮损中ｃ－ｍｙｃ、ｐ５３和ｂｃｌ－２的表达状况。结果 银屑病表皮中的ｃ－ｍｙｃ、ｐ５３和增殖细胞核抗原（ＰＣＮＡ）阳性细胞较正常皮肤明显增加,而ｂｃｌ－２阳性细胞在表皮基底层中明显减少。在ＰＣＮＡ阳性细     

红斑、丘疹及鳞屑性皮肤病

992195 Fas Bax和bcl-2蛋白在银屑病病人表皮细胞中的表达/刘振祥（北京医大三院皮肤科）…//中国皮肤性病学杂志.-1999,13（1）.-6～7 采用免疫组化方法在33例银屑病皮损标本中观察银屑病人表皮细胞中凋亡基因Fas Bax（be-cell相关基因）和凋亡抑制基因bel-2（B-cell Lymphoma/Leukemia）的作用及其相互关系。结果Fas蛋白在29/33例标本中呈阳性表达,阳性细胞呈弥漫性分布于表皮细胞各层,为胞浆、胞膜染色;Bax蛋白在23/33例标本中呈阳性表达,阳性细胞以棘层上部和颗粒层表达明显。33例bcl-2蛋白表达皆阴性,与黑色素细胞不易区别。5例正常对照中Fas及Bax皆阴性,仅部分标本在基底层细胞中呈阳性染色。结果提示促进细胞凋亡的Fas和Bax蛋白高表达,而抑制细胞凋亡的bcl-2的基本不表达与银屑病损害中表皮细胞凋亡增高有关。参5 （刘辅仁）     

系统性红斑狼疮外周血单个核细胞Fas FasL及bcl-2抗原的表达

目的探讨系统性红斑狼疮（ＳＬＥ）免疫功能失调与细胞凋亡的关系。方法应用免疫细胞化学技术对ＳＬＥ患者外周血单个核细胞（ＰＢＭＣ）上某些凋亡调节分子的表达进行了检测。结果ＳＬＥ患者ＰＢＭＣ上Ｆａｓ及ＦａｓＬ抗原均高表达,ｂｃｌ ２蛋白正常表达。结论ＳＬＥ患者体内存在较多活化的淋巴细胞,Ｆａｓ和ＦａｓＬ抗原表达异常促进了ＳＬＥ的ＰＢＭＣ凋亡。     

银屑病皮损c－erbB－1及c－erbB－2原癌基因表达及其意义

用抗ｃ－ｅｒｂＢ－１（ＥＧＦＲ）及ｃ－ｅｒｂＢ－２（Ｎｅｕ蛋白）原癌基因表达蛋白单抗及免疫组化技术，观察２０例银屑病皮损及１０例正常人皮肤。结果表明：（１）在正常人皮肤表皮中，ＥＧＦＲ基因表达蛋白主要分布在基底细胞层，Ｎｅｕ蛋白表达蛋白主要分布在棘层上部及颗粒细胞层。（２）银屑病活动性皮损表皮棘层及颗粒层ＥＧＦＲ表达增强，而Ｎｅｕ蛋白表达减弱。银屑病皮损表皮两种原癌基因表达异常对皮损形成可能起一定作用。     

银屑病皮损中细胞凋亡的原位标记检测与bcl-2的表达

目的　探讨细胞凋亡与银屑病发病的关系。方法　用末端脱氧核苷酰转移酶 (Td T)介导的 d- U TP-生物素缺口末端标记技术 (TUNEL ) ,原位检测了银屑病皮损的凋亡角朊细胞 ,应用免疫过氧化酶技术研究了正常人皮肤与银屑病皮损的 p5 3蛋白、增殖细胞核抗原 (PCNA)和 bcl- 2的表达。结果银屑病表皮各层中 ,大量角朊细胞呈现出细胞凋亡的形态学和生化特征。基底层及表皮中下部各层大量角朊细胞 PCNA染色强阳性 ,基底层中 bcl- 2阳性细胞明显减少。结论　在银屑病皮损中角朊细胞凋亡增加 ,推测可能是针对细胞过度增殖的一种稳态机理     

银屑病患者皮损表皮细胞促凋亡分子PDCD5表达的研究

目的 探讨银屑病患者表皮细胞过度增殖与细胞凋亡分化调节异常的关系.方法 寻常性银屑病患者30例,正常人对照28例.采用直接免疫荧光观察促凋亡分子PDCD5的表达状态,流式细胞仪和计算机CELL Quest软件定量分析表皮单细胞表达PDCD5的平均荧光强度和阳性率,逆转录聚合酶链反应方法检测表皮细胞表达PDCD5 mRNA的变化.结果 银屑病患者皮损增生的表皮组织细胞内PDCD5蛋白的表达明显降低,表皮单细胞表达PDCD5促凋亡分子的平均荧光强度和阳性率较正常人显著降低(P<0.01),皮损组织细胞表达PDCD5 mRNA显著低于正常人.结论 银屑病患者局部皮损表皮细胞的过度增殖与促凋亡分子PDCD5表达的下调有关,与表皮细胞的凋亡及终末分化过程的调节异常密切相关.     

Effect of vitamin D<Subscript>3</Subscript> on the increased expression of Bcl-x<Subscript>L</Subscript> in psoriasis

Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation, which may be regulated by several mechanisms including apoptosis. In this study, we detected DNA fragmentation by the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and immunohistochemically examined the expression of Bcl-x and Bax in psoriasis. We determined the expression of bcl-xL mRNA by RT-PCR, and also determined the effect of vitamin D(3) (VD3) on bcl-xL mRNA expression in cultured normal human keratinocytes by RT-PCR, and the expression of Bcl-xL in psoriatic lesions before and after topical application of VD3. A large number of TUNEL-positive cells as well as Bcl-xL - and Bax-positive cells were observed throughout the epidermis in psoriatic lesions. Whereas, in nonlesional and normal skin, only a few TUNEL-positive cells were observed and only the lower epidermis showed positive staining for Bcl-x and Bax. We also observed higher expression of bcl-xL mRNA in psoriatic lesions than in nonlesional and normal skin. The expression of bcl-xL mRNA in cultured normal human keratinocytes stimulated or not with IFN-gamma and PMA was suppressed by VD3 in a dose-dependent manner, and the expression of Bcl-xL, but not Bax, in psoriatic lesional skin decreased after topical application of VD3 for 4 weeks. In conclusion, it is suggested that the apoptotic process in psoriatic lesions is in part regulated by Bcl-xL, and decreasing the expression of Bcl-xL by treatment with VD3 might ameliorate psoriatic lesions by contributing to the completion of the apoptotic process.     

SAg作用的银屑病T细胞对表皮c-myc bcl-2及P53蛋白的影响

目的探讨链球菌超抗原与银屑病的关系,揭示银屑病患者外周血T细胞的特殊活性。方法将银屑病患者和正常人外周血T细胞及链球菌超抗原(SAg)刺激的银屑病和正常人T细胞分别与皮肤组织共同培养,免疫组化法检测不同T细胞对表皮cmyc,bcl2及P53蛋白的影响。结果正常人皮肤、银屑病患者未受累皮肤受银屑病患者T细胞作用后,表皮cmyc,bcl2及P53蛋白与正常人T细胞作用组比较有显著性差异(P均<0.05);受SAg刺激的银屑病患者T细胞对表皮cmyc,bcl2及P53蛋白的影响与未受SAg刺激组比较差异无显著性(P均>0.05),SAg非特异性活化的正常人T细胞对表皮cmyc,bcl2及P53蛋白不能产生显著影响(P均>0.05)。结论银屑病患者T细胞在外周血已处于活化状态,其活性与链球菌超抗原多克隆激活的正常人T细胞在功能上有本质区别,这一特殊的活性,可能在诱导表皮动力学紊乱及银屑病发病中发挥重要的作用。     

Alteration of the expression of Bcl-2, Bcl-x,Bax, Fas,and Fas ligand in the involved skin of psoriasis vulgaris following topical anthralin therapy

Anthralin (dithranol) is frequently used for the treatment of psoriasis. However, the mode of action of anthralin has not been completely elucidated as yet. Recent findings suggest that psoriatic keratinocytes are resistant to the apoptotic process. In this study, we examined the immunohistochemical expression of apoptosis-regulated protein in the involved psoriatic skin following topical anthralin therapy. Biopsy specimens were obtained from back skins treated with topical anthralin or white petrolatum (control) in 4 patients with psoriasis vulgaris. Immunohistochemical examination revealed that psoriatic keratinocytes expressed high levels of Bcl-x, which was significantly reduced after anthralin treatment. Bax was not detected in the epidermal keratinocytes in the petrolatum-treated skin, while it was present in the upper keratinocytes after anthralin therapy. Bcl-2 was detected only in basal layers of psoriatic epidermis following both petrolatum and anthralin application. Psoriatic keratinocytes expressed higher levels of Fas in the lower epidermis, while only weak expression was detected in anthralin-treated plaques. On the other hand, hyperproliferative keratinocytes strongly expressed Fas ligand (FasL) on their plasma membranes as well as infiltrating lymphocytes in the upper dermis. Furthermore, anthralin-treated psoriatic epidermis did not express FasL. In normal skin, keratinocytes expressed low to absent levels of Bcl-x and Bax, while Bcl-2 was detected only in melanocytes in basal layers. Neither Fas nor FasL were detected in the epidermis of normal skin. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed positive labeling on the majority of psoriatic keratinocytes through the epidermis in petrolatum-treated skin, whereas anthralin treatment markedly reduced TUNEL-positive keratinocytes. These in vivo results may reflect improvement of the psoriatic skin following effective anthralin therapy.     

降钙素基因相关肽在银屑病斑块型皮损的分泌与表达

为了解精神心理刺激诱发加重银屑病的原因,探讨神经肽在银屑病发病机理中的作用,研究了降钙素基因相关肽（ＣＧＲＰ）在银悄病皮损中的分泌与表达,并确定ＣＧＲＰ作用的靶细胞,应用特异性放射免疫反相法分析,测定３２例建党型银屑病慢性斑块型皮损组织提取液中ＣＧＲＰ的含量,用抗生物素蛋白－生物素－过氧化物酶复合法和兔抗人ＣＧＲＰ抗体进行免疫组化染色,观察ＣＧＲＰ分泌表达的部位和作用的靶细胞。结果建党型银屑病慢性