Yang Tian-Lun, Chen Mei-Fang, Luo Bai-Ling, Yu Jing, Jiang Jun-Lin, Li Yuan-Jian
Department of Cardiovascular Medicine, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):79-83. doi: 10.1007/s00210-004-0971-0. Epub 2004 Aug 14.
Previous investigations have demonstrated that asymmetric dimethylarginine (ADMA) is an important factor contributing to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in hyperlipidaemic patients. In the present study in rats treated with native low-density lipoprotein (nLDL), we addressed the question of whether the beneficial effect of fenofibrate on endothelial cells is related to reduction of the ADMA concentration. A single injection of nLDL (4 mg/kg, 48 h) markedly reduced endothelium-dependent relaxation in response to acetylcholine and the plasma level of nitrite/nitrate and increased the plasma concentrations of ADMA, malonyldialdehyde (MDA) and tumour necrosis factor-alpha (TNF-alpha). Treatment with fenofibrate (30 or 100 mg/kg) significantly reduced the inhibition of vasodilator responses to acetylcholine, decreased the elevated levels of ADMA, MDA and TNF-alpha, and enhanced the decreased level of nitrite/nitrate in the rats treated with LDL. These results suggest that the protective effect of fenofibrate on endothelial cells in rats treated with LDL may be related to the reduction of ADMA concentration.
先前的研究表明，不对称二甲基精氨酸（ADMA）是导致内皮功能障碍的一个重要因素，且非诺贝特对高脂血症患者的内皮具有保护作用。在本项针对用天然低密度脂蛋白（nLDL）处理的大鼠的研究中，我们探讨了非诺贝特对内皮细胞的有益作用是否与ADMA浓度降低有关这一问题。单次注射nLDL（4 mg/kg，48小时）显著降低了对乙酰胆碱的内皮依赖性舒张以及亚硝酸盐/硝酸盐的血浆水平，并提高了ADMA、丙二醛（MDA）和肿瘤坏死因子-α（TNF-α）的血浆浓度。用非诺贝特（30或100 mg/kg）处理可显著减轻对乙酰胆碱血管舒张反应的抑制，降低升高的ADMA、MDA和TNF-α水平，并提高用LDL处理的大鼠中降低的亚硝酸盐/硝酸盐水平。这些结果表明，非诺贝特对用LDL处理的大鼠内皮细胞的保护作用可能与ADMA浓度降低有关。
