Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.
Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.
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膳食 Omega-3 多不饱和脂肪酸可预防血管功能障碍并通过 2,3,7,8-四氯二苯并-P-二恶英减弱细胞色素 P4501A1 表达。
DOI：
10.1093/toxsci/kfw145
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Walker,MaryK
中科院分区：
文献类型：
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作者：
Wiest,ElaniF;Walsh-Wilcox,MaryT;Rothe,Michael;Schunck,Wolf-Hagen;Walker,MaryK
鱼中发现的 Omega-3 多不饱和脂肪酸 (n-3 PUFA) 可预防心血管疾病的发病率和死亡率；然而，由于担心污染物，许多人避免食用鱼类。我们测试了 n-3 PUFA 可以预防 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 引起的血管功能障碍的假设。 C57Bl/6雄性小鼠以食物或n-3 PUFA饮食喂养10周，并在每种饮食的最后2周期间暴露于媒介物或300ng/kg/d TCDD。评估了花生四烯酸 (AA) ± SKF525（P450 抑制剂）或 SQ29548（血栓烷/前列腺素 [TP] 受体拮抗剂）介导的主动脉血管收缩。分析了红细胞脂肪酸以及 n-3 和 n-6 PUFA 代谢物的表达。 测量细胞色素 P4501A1 (CYP1A1)、CYP1B1 和芳烃受体 (AHR) 的表达。 TCDD 通过增加 P450 和 TP 受体对收缩反应的贡献，显着增加饲料中 AA 介导的血管收缩。相比之下，n-3 PUFA 饮食可防止 TCDD 诱导的 AA 血管收缩增加，并使 P450 和 TP 受体的贡献正常化。尽管 TCDD 增加了食物中 AA 血管收缩剂的水平，但 n-3 PUFA 饮食可以阻止这种增加。此外，n-3 PUFA 饮食显着增加了 n-3 PUFA 衍生的血管扩张剂的水平，而 TCDD 进一步增加了这些水平。 有趣的是，n-3 PUFA 饮食显着减弱 TCDD 对 CYP1A1 的诱导作用，但对 AHR 表达没有显着影响。这些数据表明，n-3 PUFA 可以通过减少血管收缩剂、增加血管扩张剂和减弱 CYP1A1 诱导来预防 TCDD 诱导的血管功能障碍，此前已证明 CYP1A1 诱导会导致 TCDD 诱导的血管功能障碍。
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor (AHR) expression was measured. TCDD significantly increased AA-mediated vasoconstriction on a chow diet by increasing the contribution of P450s and TP receptor to the constriction response. In contrast, the n-3 PUFA diet prevented the TCDD-induced increase in AA vasoconstriction and normalized the contribution of P450s and TP receptor. Although TCDD increased the levels of AA vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3 PUFA-derived vasodilators and TCDD increased these levels further. Interestingly, the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a significant effect on AHR expression. These data suggest that n-3 PUFAs can prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors, increasing vasodilators, and attenuating CYP1A1 induction, which has been shown previously to contribute to TCDD-induced vascular dysfunction.