Adamek Anna, Jung Susanne, Dienesch Charlotte, Laser Martin, Ertl Georg, Bauersachs Johann, Frantz Stefan
Medizinische Klinik und Poliklinik I, Universität Würzburg, Germany.
Eur J Pharmacol. 2007 Sep 24;571(1):51-4. doi: 10.1016/j.ejphar.2007.05.040. Epub 2007 Jun 5.
Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses and could thereby aggravate ischemic injury. However, the role of lipoxygenase and leukotrienes in cardiac ischemia/reperfusion damage has not been well defined. Therefore, we tested the effect of ischemia reperfusion in mice with targeted deletion of 5-lipoxygenase, the enzyme converting arachidonic acid in leukotrienes. 5-LOX deficient (KO) and wild-type (WT) mice underwent 30 min of coronary artery ligation and 24 h of reperfusion in vivo. In mice with equivalent area at risk, infarct size was not significantly different between WT and KO mice (infarct/area at risk 61.7+/-3.9 vs. 55.8+/-6.6%, WT vs. KO, P=n.s.). However, neutrophil infiltration as well as tumor necrosis factor expression were increased in 5-lipoxygenase deficient mice. In summary, inhibition of 5-lipoxygenase does not affect cardiac ischemia-reperfusion injury but the post-ischemic inflammatory response.
心肌缺血可诱导心脏中5-脂氧合酶（LOX）易位并产生白三烯。白三烯会增加炎症反应，进而加重缺血性损伤。然而，脂氧合酶和白三烯在心脏缺血/再灌注损伤中的作用尚未明确界定。因此，我们测试了在5-脂氧合酶基因敲除小鼠（该酶可将花生四烯酸转化为白三烯）中缺血再灌注的效果。5-LOX基因敲除（KO）小鼠和野生型（WT）小鼠在体内经历了30分钟的冠状动脉结扎和24小时的再灌注。在梗死危险面积相当的小鼠中，WT小鼠和KO小鼠的梗死面积无显著差异（梗死面积/梗死危险面积：WT为61.7±3.9%，KO为55.8±6.6%，P值无统计学意义）。然而，5-脂氧合酶基因敲除小鼠的中性粒细胞浸润以及肿瘤坏死因子表达均增加。总之，抑制5-脂氧合酶并不影响心脏缺血-再灌注损伤，但会影响缺血后的炎症反应。
