ω-3 多不饱和脂肪酸可改善慢性肾衰竭患者的内皮功能障碍：与 eNOS 激活和氧化应激有关。

Omega 3 Polyunsaturated Fatty Acids Improve Endothelial Dysfunction in Chronic Renal Failure: Role of eNOS Activation and of Oxidative Stress.

机构信息

Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy.

Animal Facility, University of Trieste, 34127 Trieste, Italy.

出版信息

Nutrients. 2017 Aug 18;9(8):895. doi: 10.3390/nu9080895.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Collectively, these findings indicate that -3 PUFA improve endothelial dysfunction by restoring NO bioavailability in CKD.

背景

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。

方法

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。

结果

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）。