PNAS：地中海式饮食有助降血压

果蔬沙拉加橄榄油是十分健康的搭配。一个国际研究小组最新发现，这种地中海式饮食在降血压、保护心血管健康方面的益处确有科学依据。研究报告发表在美国新一期《国家科学院学报》上。

地中海地区的居民多喜欢食用水果、蔬菜、坚果和谷类等，食用油则以橄榄油和菜油为主。此前研究发现，这种饮食习惯对心血管健康大有裨益。

英国伦敦大学国王学院研究人员与欧洲同行一起报告说，他们通过动物实验发现，橄榄油、坚果中富含的不饱和脂肪酸与蔬菜中的氮氧化合物会发生反应，产生硝基脂肪酸。这种物质会抑制动物体内一种与心血管疾病有密切关系的酶发挥作用，并帮助调节血压。研究者通过制作一种Cys521Ser sEH redox-dead knockin的小鼠模型，在Ang II诱导的高血压模型中， electrophilic lipid 10-nitro-oleic acid (NO2-OA) 对野生型小鼠具有明显的降压作用，但对这种Knockin小鼠是无效的。由此可知，NO2-OA介导的降压效应可能通过抑制sEH起作用。

领导这项研究的伦敦大学国王学院教授菲利普·伊顿说，这一研究结果有助于解释地中海式饮食保护心血管健康的具体机制。这种饮食方式对降低中风、心衰和心脏病风险均有益处。

Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redox-dead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO2-OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO2-OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO2-OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.

原始出处：
Charles RL, Rudyk O, Prysyazhna O, Kamynina A, Yang J, Morisseau C, Hammock BD, Freeman BA, Eaton P.Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8167-72.