英國倫敦大學(xué)國王學(xué)院和美國的科研人員發(fā)現(xiàn)了一種機(jī)制，不飽和脂肪酸與富含亞硝酸鹽和硝酸鹽的蔬菜——諸如橄欖油和多葉綠色蔬菜——結(jié)合起來的飲食通過這種機(jī)制可以使小鼠免于患上高血壓。相關(guān)文章發(fā)表于2014年5月19日的《PNAS》雜志上。

　　Philip Eaton及其同事研究了硝基脂肪酸降低血壓的過程，硝基脂肪酸是由不飽和脂肪酸與含氮化合物反應(yīng)產(chǎn)生的。可溶性的酶環(huán)氧化物酶(sEH)被硝基脂肪酸抑制，從而引起了血壓的下降。

　　為了確定抑制可溶性環(huán)氧化物酶(sEH)是否足以在活體中降低血壓，這組作者培育了可溶性環(huán)氧化物酶(sEH)能夠抵抗硝基脂肪酸抑制的突變小鼠。在野生型小鼠體內(nèi)降低血壓的一種硝基脂肪酸可溶性環(huán)氧化物酶(sEH)抑制劑對攜帶這種突變的小鼠沒有作用。這種抑制劑保護(hù)了野生型小鼠的心臟免受高血壓小鼠模型所受到的損傷，但是抗可溶性環(huán)氧化物酶(sEH)抑制劑突變種沒有受到保護(hù)，當(dāng)小鼠食用見于地中海飲食的某種硝基脂肪酸前體的時候，可溶性環(huán)氧化物酶(sEH)在野生型小鼠體內(nèi)被抑制了，但是在突變型小鼠體內(nèi)未被抑制。

　　這組作者說，這些發(fā)現(xiàn)可能為地中海飲食對心血管有益提供一種解釋，在地中海飲食中，來自橄欖油或堅(jiān)果的不飽和脂肪酸與來自多葉綠色蔬菜的亞硝酸鹽產(chǎn)物聯(lián)合起來提高了硝基脂肪酸的水平，后者通過抑制可溶性環(huán)氧化物酶(sEH)降低了血壓。

　　原文摘要：

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Rebecca L. Charles, Olena Rudyk, Oleksandra Prysyazhna, Alisa Kamynina, Jun Yang,Christophe Morisseau, Bruce D. Hammock, Bruce A. Freeman and Philip Eaton

　　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.