中华皮肤科杂志 ›› 2008, Vol. 41 ›› Issue (9): 605-608.

• 论著 • 上一篇    下一篇

几种IAP蛋白及其相关因子在蕈样肉芽肿中的表达及NB-UVB的作用

赵恒光 李惠 杨和荣   

  1. 重庆医科大学附属第一医院皮肤科 重庆医科大学附属第一医院皮肤科
  • 收稿日期:2007-11-08 修回日期:2007-12-17 发布日期:2008-09-15
  • 通讯作者: 赵恒光 E-mail:zhgvip@163.com

Expressions of two inhibitors of apoptosis proteins and their related factors in mycosis fungoides and the effect of NB-UVB irradiation on them

  

  • Received:2007-11-08 Revised:2007-12-17 Published:2008-09-15

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摘要： 目的 探讨生存素（Survivin）和Livin两种凋亡抑制蛋白（IAP）及其相关因子Bcl-xl和Caspase-3在蕈样肉芽肿（MF）中的表达情况和窄谱中波紫外线（NB-UVB）的干预作用。方法 采用免疫组化SABC法测定生存素、Livin、Bcl-xl和Caspase-3在MF皮损中的表达，用TUNEL法和原位杂交技术检测NB-UVB治疗前后四种因子mRNA的转录水平和细胞凋亡指数的变化。结果 在MF红斑期、斑块期和肿瘤期，生存素的表达阳性率分别为40.00%、75.00%、77.78%；Bcl-xl为60.00%、68.75%、88.89%，二者在正常皮肤均无表达。Livin在MF三期中阳性率依次为40.00%、25.00%和44.44%；Caspase-3为60.00%、43.75％和22.22％，二者均与正常皮肤相似。NB-UVB治疗后，MF中凋亡细胞显著增多（t = 6.49，P < 0.001），生存素mRNA和Bcl-xl mRNA的表达较照射治疗前有显著降低（P < 0.10），而Caspase-3 mRNA的表达增加（P < 0.10），Livin mRNA的表达在照射治疗前后无显著变化（P > 0.10）。结论 生存素、Bcl-xl和Caspase-3可能参与MF中T淋巴细胞凋亡障碍的调节过程，与MF的发病有关。NB-UVB对MF的治疗作用可能与其抑制生存素mRNA和Bcl-xl mRNA的转录，降低IAP蛋白水平，增加Caspase-3的转录，进而增强MF肿瘤细胞的凋亡有关。

关键词: 蕈样肉芽肿, 凋亡抑制蛋白, 窄谱中波紫外线

Abstract: Objective To observe the expressions of two inhibitors of apoptosis proteins （IAPs）, survivin and livin, as well as their related factors, Bcl-xl and Caspase-3 in mycosis fungoides （MF）, along with the effects of NB-UVB irradiation on them. Methods Totally, 30 patients with MF （5 at erythema stage, 16 at plaque stage and 9 at tumor stage） collected from 1995 to 2007 were included into this study. Of the patients, 11 received the treatment with NB-UVB irradiation. Tissue samples were resected from 30 untreated patients, 11 irradiated patients and 10 normal human controls. SABC immunohistochemistry （IHC） stain was used to evaluate the protein expression of survivin, livin, Bcl-xl and caspase-3 in these samples. Also, the mRNA expression of these four factors and cell apoptosis were detected by hybridization in situ （ISH） and terminal deoxynucleotidyl transferase （TdT）-mediated dUTP-fluorescence nick end labeling （TUNEL stain） respectively in the samples from 11 patients before and after NB-UVB irradiation. Results In samples of erythema-stage MF, plaque-stage MF and tumor-stage MF, the positivity rate was 40.00%, 75.00%, 77.78% for survivin respectively, 60.00%, 68.75%, 88.89% for Bcl-xl respectively, 40%, 25%, 44.44% for livin respectively, and 60.00%, 68.75%, 88.89% for caspase-3 respectively. No expression of survivin or Bcl-xl was observed in normal controls, while the expression of livin and caspase-3 was similar between MF and control samples. After NB-UVB irradiation, an increase was noticed in the count of apoptosis cells （t = 6.49, P < 0.001） and mRNA expression of caspase-3 （P < 0.10）, while a decrease in the mRNA expression of survivin and Bcl-xl in MF tissues, and no changes occurred to the mRNA expression of livin （P > 0.10）. Conclusions Survivin, Bcl-xl and caspase-3 may be associated with the pathogenesis of MF by regulating the cell apoptosis of T lymphocytes. NB-UVB could suppress the mRNA expression of survivin and Bcl-xl, lower the levels of IAP, enhance the transcription of caspase-3, and accelerate the apoptosis of tumor cells, which may partly explain the mechanism of therapeutic effect of NB-UVB in MF.

Key words: mycosis fungoides, inhibitor of apoptosis protein, narrow-band ultra-violet B