Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation
Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation
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DOI：
10.1016/j.resuscitation.2007.06.031
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发表时间：
2008-01-01
期刊：
影响因子：
6.5
通讯作者：
Alkayed, Nabil J.
中科院分区：
文献类型：
--
作者：
Hutchens, Michael P.;Nakano, Takaaki;Alkayed, Nabil J.
P450类二十烷酸环氧二十碳三烯酸（Epoxyeicosatrienoic Acids，EEP）由细胞色素P450花生四烯酸环氧合酶产生，并通过多种途径代谢，包括可溶性环氧化物水解酶（soluble epoxide hydrolase，sEH）。sEH的药理学抑制和基因缺失可保护脑和心脏的缺血/再灌注损伤，以及保护肾脏的高血压相关终末器官损伤。我们检验了sEH基因缺失可改善由心脏骤停（CA）和复苏诱导的短暂全身缺血后的存活率、肾功能恢复和病理性缺血性肾损伤的假设。使具有sEH靶向缺失的小鼠（sEH敲除，sEHKO）和C57 B1/6野生型对照小鼠经受10分钟CA，随后进行心肺复苏（CPR）。CA/CPR后10 min和24 h，野生型小鼠的存活率分别为93%和80%（n = 15）。出乎意料的是，sEHKO小鼠的存活率显著低于WT，CA/CPR后只有56%的sEHKO小鼠存活10分钟（n= 15，与WT相比p= 0.014），没有小鼠存活24小时（与WT相比p < 0.0001）。我们得出结论，sEH在心血管调节中起着重要作用，降低sEH水平或功能会降低心脏骤停的生存率。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n = 15). Unexpectedly, survival in sEHKO mice was significantly lower than WT Only 56% of sEHKO mice survived for 10 min (n= 15, p= 0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p < 0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest. (c) 2007 Elsevier Ireland Ltd. All rights reserved.