NF-κB在高浓度葡萄糖、TNF-α、IL-1β介导的血管内皮细胞损害中的作用  

The role of transcription factor NF- κB in vascular endothelial cell impairment induced by high glucose,TNF-α and IL-1β

作　　者：肖彧君[1] 黄爱龙[2] 李春霖[1] 邓华聪[3] 向明确[2] 唐霓[2] 

机构地区：[1]中国人民解放军总医院内分泌科 [2]重庆医科大学肝炎研究所 [3]重庆医科大学附属第一医院内分泌科

出　　处：《中华内分泌代谢杂志》2005年第4期310-312,共3页Chinese Journal of Endocrinology and Metabolism

基　　金：国家"十五"863资助项目(2001AA217121);国家自然科学基金资助项目(30070297)

摘　　要：目的研究核转录因子κB(NFκB)在高糖、肿瘤坏死因子(TNFα)、白细胞介素1β(IL1β)诱导ECV304血管内皮细胞损害中的作用。方法以构建含NFκB抑制物IκBα突变体(IκBαM)的重组腺病毒感染ECV304细胞,用Western印迹、凝胶电泳迁移率实验(EMSA)、四甲基偶氮唑盐(MTT)等方法研究NFκB在高糖、TNFα、IL1β介导血管内皮细胞损害中的作用。结果TNFα可诱导ECV304细胞的IκBα降解和NFκB的激活(P<0.01),而对ECV304/IκBαM细胞则无此作用;高糖可导致ECV304细胞NFκB的激活(P<0.05),而对ECV304/IκBαM细胞则无此作用;单独使用高糖、TNFα、IL1β导致ECV304细胞活力的降低(均P<0.01),而ECV304/IκBαM细胞可抵抗这些因素对细胞的损害(均P<0.05)。结论高糖、TNFα、IL1β可致血管内皮细胞活力降低,IκBα能有效抑制上述有害因素导致的ECV304细胞NFκB的过度活化,抵抗内皮细胞的损害。抑制NFκB活性可能有助于保护血管内皮细胞的功能。Objective To investigate the role of NF-κB in high glucose （HG） and cytokines （TNF-α and IL-1β）-induced impairment of ECV-304 cells （ vascular endothelial cell line）. Methods Recombinant adenovirus containing NF-κB supper-repressor IκBαM with mutant IκBα was constructed. Western blot, electrophoretic mobility shift assay （ EMSA ） and thiazolyl blue viability assay were applied in this study. Results TNF-α-induced IκBα degradation and NF-κB activation （ P〈0.01 ） were found in ECV-304 cells but not in ECV-304/IκBαM cells ; and HG-induced NF-κB activation （ P〈0.05 ） was also found in ECV-304 cells but not in ECV-304/IκBαM cells intected with IκBαM recombinant adenovirus. The viability of ECV-304 cells incubated with HG, TNF-α or IL-1β was obviously decreased （ all P〈0.01 ） , but ECV-304/IκBαM cells could resist the effect of HG and cytokines on cell viability （ all P〈0.05 ）. Conclusion HG and cytokines （ TNFα, IL-β） can decrease the viability of vascular endothelial cells. IκBα can effectually inhibit the excessive activation of NF-κB in ECV-304. Inhibition of NF-κB activity can protect vascular endothelial cells from the cytotoxicity of HG and the cytokines.

关 键 词：NF-ΚB 葡萄糖 细胞损害 细胞因子 血管内皮细胞 肿瘤坏死因子 白细胞介素1Β 糖尿病 

分 类 号：R587.2[医药卫生—内分泌]