The effects of omega-3 PUFA on vascular function

我们测试了n-3 PUFAs是否通过激活Nrf2（抗氧化基因的主要转录因子）显示抗氧化活性。C57BL/6或Nrf2-/-小鼠喂食鱼油饲料。鱼油饮食显著增加了C57BL/6小鼠主动脉血红素氧合酶-1 （HO-1）的表达和内皮依赖性血管舒张，而Nrf2-/-小鼠则无此作用。此外，我们观察到4-羟基己烯醛（4-HHE）， n-3 PUFA过氧化的最终产物，在C57BL/6小鼠的主动脉中显著增加，并伴有主动脉内DHA的增加，而不是EPA的增加。人脐静脉内皮细胞用DHA或EPA孵育。我们发现DHA显著增加细胞内4-HHE、细胞核表达和Nrf2的DNA结合，而EPA没有。DHA和4-HHE均增加了HO-1等Nrf2靶基因的表达。此外，DHA可以防止氧化诱导的细胞损伤，但这种作用被Nrf2的siRNA所消除。

We tested whether n-3 PUFAs showed antioxidant activity through the activation of Nrf2, a master transcriptional factor for antioxidant genes. C57BL/6 or Nrf2-/- mice were fed a fish-oil diet. Fish-oil diet significantly increased the expression of heme oxygenase-1 (HO-1), and endothelium-dependent vasodilation in the aorta of C57BL/6 mice, but not in Nrf2-/- mice. Furthermore, we observed that 4-hydroxy hexenal (4-HHE), an end-product of n-3 PUFA peroxidation, was significantly increased in the aorta of C57BL/6 mice, accompanied by intra-aortic predominant increase in DHA rather than that in EPA. Human umbilical vein endothelial cells were incubated with DHA or EPA. We found that DHA, but not EPA, markedly increased intracellular 4-HHE, and nuclear expression and DNA binding of Nrf2. Both DHA and 4-HHE also increased the expressions of Nrf2 target genes including HO-1. Furthermore, DHA prevented oxidant-induced cellular damage and this effect was disappeared by the siRNA of Nrf2.