Niu N, Yu Y H, Wang Y, Wang L J, Li Q, Guo L M
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Mol Biol Rep. 2009 Jul;36(6):1275-81. doi: 10.1007/s11033-008-9309-1. Epub 2008 Jul 12.
Combined treatment with niacin and chromium has been found to have a protective effect against oxidative damage to different tissues of hyperlipidemic rats. But its effects on vascular endothelial dysfunction are less clear. This study was performed to investigate the effect of combined treatment with niacin and chromium on vascular endothelial dysfunction, with the aim of gaining insight to the mechanisms by detecting the expression levels of ox-LDL and LOX-1. Twenty-four male, 4-week-old Wistar rats were randomly divided into three groups: control group (CG; n = 8), high-fat group (HF; n = 8), and drug control group (DG; n = 8). In CG group, rats were fed with pellet chow. In HF group, rats were fed with high-fat diet for 12 weeks. In DG group, rats were fed with the same high-fat diet and treated with CrCl(3) x 6 H(2)O (250 microg/kg days) and niacin (100 mg/kg days) by gavage technique for 12 weeks. At the end of the 12th week, samples from aorta and blood were collected. In HF group, the serum levels of total cholesterol (TC), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL) and endothelin (ET) were higher, whereas the levels of high-density lipoprotein (HDL), serum NO were lower than those in CG group. The levels of serum TC, LDL, ox-LDL and ET decreased and HDL, NO levels increased in DG group when compared with HF group. The levels of LOX-1, ICAM-1 were also observed in abdominal artery. In HF group, the protein and mRNA expression of LOX-1, ICAM-1 were elevated comparing with CG group. In DG group, the protein and mRNA expression of LOX-1, ICAM-1 were decreased obviously, but still differed significantly from those in CG group. ox-LDL was related positively to TC, LDL, ET, ICAM-1 and LOX-1, but related negatively to NO and HDL. These findings indicated that combined treatment with niacin and chromium has potential therapeutic protection of endothelial function by down-regulating ox-LDL/LOX-1 signaling pathway.
已发现烟酸和铬联合治疗对高脂血症大鼠不同组织的氧化损伤具有保护作用。但其对血管内皮功能障碍的影响尚不清楚。本研究旨在探讨烟酸和铬联合治疗对血管内皮功能障碍的影响，通过检测氧化型低密度脂蛋白（ox-LDL）和凝集素样氧化型低密度脂蛋白受体1（LOX-1）的表达水平来深入了解其机制。将24只4周龄雄性Wistar大鼠随机分为三组：对照组（CG；n = 8）、高脂组（HF；n = 8）和药物对照组（DG；n = 8）。CG组大鼠喂饲普通颗粒饲料。HF组大鼠喂饲高脂饮食12周。DG组大鼠喂饲相同的高脂饮食，并通过灌胃技术给予三氯化铬（CrCl₃·6H₂O）（250微克/千克·天）和烟酸（100毫克/千克·天）治疗12周。在第12周结束时，采集主动脉和血液样本。HF组血清总胆固醇（TC）、低密度脂蛋白（LDL）、氧化型低密度脂蛋白（ox-LDL）和内皮素（ET）水平较高，而高密度脂蛋白（HDL）、血清一氧化氮（NO）水平低于CG组。与HF组相比，DG组血清TC、LDL、ox-LDL和ET水平降低，HDL、NO水平升高。还观察了腹主动脉中LOX-1、细胞间黏附分子-1（ICAM-1）的水平。HF组中，与CG组相比，LOX-1、ICAM-1的蛋白和mRNA表达升高。DG组中，LOX-1、ICAM-1的蛋白和mRNA表达明显降低，但仍与CG组有显著差异。ox-LDL与TC、LDL、ET、ICAM-1和LOX-1呈正相关，但与NO和HDL呈负相关。这些发现表明，烟酸和铬联合治疗通过下调ox-LDL/LOX-1信号通路对内皮功能具有潜在的治疗保护作用。
