Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy.
Animal Facility, University of Trieste, 34127 Trieste, Italy.
Nutrients. 2017 Aug 18;9(8):895. doi: 10.3390/nu9080895.
Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether -3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial nitric oxide synthase (eNOS) function and oxidative stress.
5/6 nephrectomized male Wistar rats (CKD; = 10) and sham operated animals (SHAM; = 10) were treated for 6 weeks with standard diet. An additional group of CKD rats were fed an -3 PUFA enriched diet (CKD + PUFA; = 10). We then measured endothelium-dependent (EDD) and -independent vasodilation, markers of endothelial function and of oxidative stress in thoracic aortas.
Compared to SHAM, in CKD aortas EDD and eNOS expression were reduced ( < 0.05) and 3-nitrotyrosine levels were increased, while expression of NADPH oxidase subunits NOX4 and p22 was similar. In-vitro incubation with Tiron failed to reverse endothelial dysfunction in CKD. In CKD + PUFA, EDD improved ( < 0.05) compared with CKD rats, while blockade of eNOS by L-NAME worsened EDD. These effects were accompanied by increased ( < 0.05) eNOS and reduced ( < 0.05) expression of NOX4 and 3-nitrotyrosine levels.
Collectively, these findings indicate that -3 PUFA improve endothelial dysfunction by restoring NO bioavailability in CKD.
内皮功能障碍是慢性肾脏病（CKD）的一个关键血管改变。ω-3 多不饱和脂肪酸（PUFA）可减少血管氧化应激和炎症。我们研究了 ω-3 PUFA 是否可以通过改善内皮型一氧化氮合酶（eNOS）功能和氧化应激来逆转 CKD 中的内皮功能障碍。
5/6 肾切除雄性 Wistar 大鼠（CKD；n = 10）和假手术对照动物（SHAM；n = 10）用标准饮食治疗 6 周。另外一组 CKD 大鼠用富含 ω-3 PUFA 的饮食喂养（CKD + PUFA；n = 10）。然后我们测量了胸主动脉中的内皮依赖性（EDD）和非依赖性血管舒张、内皮功能和氧化应激的标志物。
与 SHAM 相比，在 CKD 主动脉中 EDD 和 eNOS 表达减少（<0.05），3-硝基酪氨酸水平升高，而 NADPH 氧化酶亚基 NOX4 和 p22 的表达相似。在体外用 Tiron 孵育未能逆转 CKD 中的内皮功能障碍。在 CKD + PUFA 中，EDD 与 CKD 大鼠相比有所改善（<0.05），而用 L-NAME 阻断 eNOS 则使 EDD 恶化。这些作用伴随着 eNOS 的增加（<0.05）和 NOX4 和 3-硝基酪氨酸水平的降低（<0.05）。
总的来说，这些发现表明 ω-3 PUFA 通过恢复 CKD 中 NO 的生物利用度来改善内皮功能障碍。
