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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia.
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Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia.

机译：可溶性环氧化物水解酶在对脑缺血的性别特异性血管反应中的作用。

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摘要

Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sEHKO) mice. Male, female, and ovariectomized female WT and sEHKO mice were subjected to 2-h middle cerebral artery occlusion (MCAO) and infarct size was measured at 24 h of reperfusion. Laser-Doppler cortical perfusion during MCAO was compared among groups and differences in cortical blood flow rates were confirmed using in vivo quantitative optical microangiography. Cerebrovascular expression and activity of sEH and plasma 14,15-DHET were lower in WT female than male mice, and blood flow during MCAO was higher and infarct size was smaller in WT female compared with male mice. Sex differences in cerebral blood flow and ischemic damage were abolished after ovariectomy and were absent in sEHKO mice. We conclude that sEH is an important mechanism underlying sex-linked differences in blood flow and brain damage after cerebral ischemia.
机译：可溶性环氧水解酶（sEH）是血管扩张性类二十烷酸（称为环氧二十碳三烯酸（EETs））代谢中的关键酶，具有两性性质，并被雌激素抑制。我们确定了局灶性脑缺血期间血流的性别差异是否与sEH有关。在雄性和雌性野生型（WT）和sEH基因敲除（sEHKO）小鼠中确定了大脑中可溶性环氧化物水解酶的表达，脑血管中的水解酶活性和血浆中的14,15-二羟基二十碳三烯酸（14,15-DHET）。对雄性，雌性和卵巢切除的雌性WT和sEHKO小鼠进行2 h脑中动脉闭塞（MCAO），并在再灌注24 h时测量梗塞面积。比较各组之间MCAO期间的激光多普勒皮质灌注，并使用体内定量光学微血管造影术确认皮质血流速率的差异。与雌性小鼠相比，雌性小鼠的脑血管表达和sEH及血浆14,15-DHET活性较低，雌性小鼠的MCAO期间血流较高，梗死面积较小。卵巢切除术后消除了脑血流和缺血性损伤的性别差异，而在sEHKO小鼠中则没有。我们得出的结论是，sEH是导致脑缺血后血流和脑损伤性别相关差异的重要机制。

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