高糖上调内皮细胞间黏附分子1和血管细胞黏附分子1表达的作用机制  

Mechanism underlying up-regulation of ICAM-1 and VCAM-1expressions induced by high glucose in endothelial cells

作　　者：农善伟[1] 柯丽琴[2] 张小勇[2] 黄秀清[2] 满永[2] 王抒[2] 黎健[2] 宁应之[1] 

机构地区：[1]西北师范大学,兰州730070 [2]卫生部北京医院老年医学研究所

出　　处：《中国心血管杂志》2010年第3期219-222,共4页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金项目(30440065、30572082、30870273);北京市自然科学基金资助项目(7052059)

摘　　要：目的探讨高糖上调内皮细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）表达的作用机制。方法高浓度葡萄糖（20mmol／L）处理分离培养的人脐静脉内皮细胞（HUVECs），以2′-7′-二氯荧光素双醋酸盐（DCFH—DA）标记流式细胞仪检测细胞内活性氧（ROS）。Western blot分析细胞内抑制性蛋白κB（IκB）和核转录因子-κB（NF—κB）蛋白表达和磷酸化水平。免疫荧光法检测NF—κB的活化。结果高糖处理HUVECs后，伴随ROS的显著升高，IκB蛋白明显下调，磷酸化的IκB和NF—κB均增多，使NF—κB移位至细胞核内，导致ICAM-1、VCAM-1的表达明显增强。结论高糖通过刺激ROS的产生和NF—κB的活化上调内皮细胞ICAM-1和VCAM-1黏附因子的表达。Objective To investigate the mechanism underlying up-regulation of ICAM-1 and VCAM-1 expression induced by high glucose in endothelial cells. Methods Cultured human umbilical vein endothelial cells （HUVECs）were treated with 20 mmol/L glucose, and cellular reactive oxygen species （ROS） level was detected by flow cytometry. Western blot was applied to analyse expression and phosphorylation of IκB and NF-κB. The activation of NF-κB was measured by immunofluorescence. Results Treatment of HUVECs with 20 mmol/L glucose decreased IκB level and stimulated the phosphorylation of IκB and NF-κB, and accompanied by increased ROS level. NF-κB was translocated into nucleus where NF-κB up-regulated the expressions of inflammatory factors such as ICAM-1 and VCAM-1. Conclusions High glucose upregulates the expressions of ICAM-1 and VCAM-1 via the stimulation of ROS generation and the activation of NF-κB pathway.

关 键 词：葡萄糖 内皮细胞 活性氧 细胞黏附分子 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]