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  

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

作　　者：王哲[1,2] 张殿宝[1] 施萍[3] 刘晓玉[1] 庞希宁[1] 

机构地区：[1]中国医科大学 卫生部细胞生物重点实验室 干细胞与再生医学研究室,辽宁沈阳110001 [2]中国医科大学盛京医院输血科,辽宁沈阳110001 [3]中国医科大学附属第一医院全科医学教研室,辽宁沈阳110001

出　　处：《基础医学与临床》2013年第11期1422-1425,共4页Basic and Clinical Medicine

基　　金：国家重点基础研究发展计划(2012CB518103);国家自然科学基金(81370883);辽宁省科学技术计划(2012225080);沈阳市科学技术计划(F11-262-9-01)

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,AGEBSA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。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 （50 μmol/L probucol ＋ 100 mg/L AGE-BSA）and high probucol group（ 100 μmol/L probucol ＋ 100 mg/L AGE-BSA）. The content of malondialdehyde （MDA）, the activities of superoxide dismutase （SOD） in Fibroblasts were detected. The protein level of NF-κB P65 and ICAM-1 was also measured by Western blot. Results 1） The content of malondialdehyde（MDA） was markedly increased, the activities of superoxide dismutase （SOD） were markedly decreased in AGE-BSA group, the protein level of NF-κB P65 and ICAM-1 was markedly increased in AGE-BSA group. 2 ） Probucol significantly 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. Conclusions Protective effect of probucol on dysfunction of fibroblasts induced by AGEs may be related to its effect on the suppressing the activation of NF-κB and subsequent expression of ICAM-1.

关 键 词：普罗布考 糖基化终末产物 成纤维细胞 细胞黏附分子1 

分 类 号：R965[医药卫生—药理学]