Effect of NF-κB Decoy Oligodeoxynucleotide on LPS/High-Fat Diet-Induced Atherosclerosis in an Animal Model

Effect of NF-κB Decoy Oligodeoxynucleotide on LPS/High-Fat Diet-Induced Atherosclerosis in an Animal Model
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DOI:
10.1111/j.1742-7843.2010.00617.x
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发表时间:
2010-12-01
影响因子:
3.1
通讯作者:
Park, Kwan-Kyu
Park, Kwan-Kyu
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Soo-Jung;Park, Ji-Hyun;Park, Kwan-Kyu

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动脉粥样硬化是发生在动脉壁的慢性炎症过程,很大程度上是由于炎症细胞的聚集。本研究旨在探讨核因子-kappaB诱骗寡核苷酸(ODN)在动脉粥样硬化动物模型中的作用。小鼠接受腹腔注射。每周3次注射脂多糖(LPS,2 mg/kg)诱导动脉粥样硬化改变,同时给予致动脉粥样硬化饲料12周。尾静脉注射核因子-kappaB诱骗寡核苷酸(0.4 mg/kg)。NF-kappa B诱骗寡核苷酸可降低脂多糖/脂肪诱导的小鼠的促炎性细胞因子、肿瘤坏死因子α和白介素1β,以及炎症标志物血管黏附分子1和细胞间黏附分子1。此外,NF-kappa B诱骗ODN治疗组小鼠肝纤维化相关蛋白、转化生长因子-β1和纤维连接蛋白的表达明显低于未治疗的脂多糖/脂肪诱导组。提示核因子-kappa B诱骗ODN对动脉粥样硬化小鼠促炎症细胞因子和细胞黏附分子的表达可能具有抑制作用。
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)-kappa B 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-kappa B decoy ODN (0.4 mg/kg) was injected into the tail vein. Treatment with NF-kappa B decoy ODN decreased pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 beta 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)-beta 1 and fibronectin were markedly decreased in the mice treated with NF-kappa B decoy ODN compared with the LPS/Fat-induced mice without decoy ODN treatment. These data suggest that NF-kappa B decoy ODN may exert an inhibitory effect on the expression levels of pro-inflammatory cytokines and cell adhesion molecules in atherosclerotic mice.