基础医学与临床 ›› 2013, Vol. 33 ›› Issue (11): 1422-1425.

• 间充质干细胞与皮肤损伤修复专题 • 上一篇    下一篇

普罗布考减轻糖基化终末产物诱导人真皮成纤维细胞NF-κB活化及ICAM-1表达

王哲1,张殿宝2,施萍3,刘晓玉2,庞希宁2   

  1. 1. 中国医科大学附属盛京医院
    2. 中国医科大学
    3. 中国医科大学附属第一医院
  • 收稿日期:2013-08-27 修回日期:2013-09-17 出版日期:2013-11-05 发布日期:2013-10-28
  • 通讯作者: 庞希宁 E-mail:pangxining@126.com
  • 基金资助:
    973

Probucol inhibits NF-κB activation and ICAM-1 expression in human dermal fibroblasts induced by advanced glycation end products

1,Dian-Bao ZHANGping SHI1,Xiao-Yu LIU3,   

  • Received:2013-08-27 Revised:2013-09-17 Online:2013-11-05 Published:2013-10-28

摘要: 目的 观察普罗布考对糖基化终末产物(AGEs)诱导成人真皮成纤维细胞(Fb)细胞核因子κB(NF-κB)活化与ICAM-1表达的影响。方法 取足部创面皮肤进行Fb培养。实验分4组:对照组、AGE-BSA作用组(AGE-BSA浓度100 mg /L)、高浓度普罗布考组(100μmol /L普罗布考+100 mg /L AGE-BSA)、低浓度普罗布考组(50μmol /L普罗布考+100 mg /L AGE-BSA)。光镜下观察细胞形态学改变,测定细胞中丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活性,应用Western blot检测细胞核NF-κB P65蛋白和总ICAM-1蛋白表达。结果1)与对照组相比,AGE-BSA作用组Fb形态改变,核蛋白NF-κB P65表达明显增加(P<0.01),细胞总ICAM-1表达明显升高(P<0.05);普罗布考可在不同程度纠正上述变化。2)普罗布考显著抑制AGE-BSA诱导Fb MDA 含量增加和 SOD活性下降(P<0.05);普罗布考能抑制AGE-BSA诱导Fb NF-κB 和ICAM-1蛋白表达水平上升。结论 普罗布考对AGE-BSA诱导Fb的保护作用可能是通过抑制NF-κB活化以及减低ICAM-1表达来实现的。

关键词: 普罗布考, 糖基化终末产物, 成纤维细胞, 细胞粘附分子1

Abstract: Objective To investigate the influence of Probucol on the activation of NF –κB and expression of ICAM-1 in dermal fibroblasts induced by advanced glycation end products (AGEs). Methods Fibroblasts were isolated and cultured in vitro, and then divided into 4 groups: control group, AGE-BSA group, low Probucol group(50μmol /L Probucol+100 mg /L AGE-BSA)and high Probucol group(100μmol /L Probucol+100 mg /L AGE-BSA).The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) in Fibroblasts were detected. The Protein levels of NF – κB p65 and ICAM-1 were also measured by Western blot. Results (1) Compared with control group, the content of malondialdehyde (MDA) markedly was increased, the activities of superoxide dismutase (SOD) markedly were decreased in AGE-BSA group, the Protein levels of NF – κB P65 and ICAM-1 were markedly increased in AGE-BSA group. (2) Probucol markedly inhibited the decrease in SOD activity, the increase in the content of MDA in fibroblasts induced by AGE-BSA. In addition, the over-expression of NF–κB p65 and ICAM-1 in fibroblasts was inhibited markedly by Probucol. Conclusion Protective effect of probucol on dysfunction of fibroblasts induced by AGEs may be related with its effect on the suppressing the activation of NF–κB and subsequent expression of ICAM-1.

Key words: Probucol, advanced glycation end products, fibroblasts, Intercellular adhesion molecule-1