Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu, South Korea.
Basic Clin Pharmacol Toxicol. 2010 Dec;107(6):925-30. doi: 10.1111/j.1742-7843.2010.00617.x.
Atherosclerosis is a chronic inflammatory process occurring in the walls of arteries, in large part due to the accumulation of inflammatory cells. This study was conducted to determine the effect of nuclear factor (NF)-κB decoy oligodeoxynucleotide (ODN) in an atherosclerosis animal model. The mice received i.p. injections of lipopolysaccharide (LPS, 2 mg/kg) three times a week to induce atherosclerotic change, and fed an atherogenic diet for 12 weeks. NF-κB decoy ODN (0.4 mg/kg) was injected into the tail vein. Treatment with NF-κB decoy ODN decreased pro-inflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β and inflammatory markers, vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, in the LPS/Fat-induced mice. In addition, the expression of proteins related to fibrosis, transforming growth factor (TGF)-β1 and fibronectin were markedly decreased in the mice treated with NF-κB decoy ODN compared with the LPS/Fat-induced mice without decoy ODN treatment. These data suggest that NF-κB decoy ODN may exert an inhibitory effect on the expression levels of pro-inflammatory cytokines and cell adhesion molecules in atherosclerotic mice.
动脉粥样硬化是一种发生在动脉壁的慢性炎症过程,在很大程度上是由于炎症细胞的积累。本研究旨在确定核因子(NF)-κB 寡脱氧核苷酸(ODN)在动脉粥样硬化动物模型中的作用。小鼠每周接受腹腔注射脂多糖(LPS,2mg/kg)三次,以诱导动脉粥样硬化变化,并给予致动脉粥样硬化饮食 12 周。NF-κB 寡脱氧核苷酸(ODN)(0.4mg/kg)尾静脉注射。NF-κB 寡脱氧核苷酸(ODN)治疗可降低 LPS/Fat 诱导的小鼠促炎细胞因子 TNF-α 和 IL-1β 以及炎症标志物 VCAM-1 和 ICAM-1 的表达。此外,与未用寡脱氧核苷酸治疗的 LPS/Fat 诱导的小鼠相比,NF-κB 寡脱氧核苷酸治疗的小鼠中与纤维化相关的蛋白质 TGF-β1 和纤维连接蛋白的表达明显降低。这些数据表明,NF-κB 寡脱氧核苷酸可能对动脉粥样硬化小鼠的促炎细胞因子和细胞黏附分子的表达水平发挥抑制作用。