CYP2J2 and EETs Protect Against Lung Ischemia/Reperfusion Injury via Anti-Inflammatory Effects in Vivo and in Vitro
CYP2J2 and EETs Protect Against Lung Ischemia/Reperfusion Injury via Anti-Inflammatory Effects in Vivo and in Vitro
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DOI：
10.1159/000374011
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Wang, Jianing
中科院分区：
文献类型：
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作者：
Chen, Wenshu;Yang, Shijiang;Wang, Jianing
背景：损伤性炎症反应在肺缺血/再灌注损伤（LIRI）的发生发展中至关重要。细胞色素P450环氧合酶2 J2（CYP 2 J2）将花生四烯酸代谢为环氧二十碳三烯酸（E3），E3对心血管系统发挥抗炎作用。因此，我们假设CYP 2 J2过表达和用外源性雌二醇预处理可能具有降低LIRI的潜力。方法：采用夹闭大鼠左肺门60 min，再灌注2 h的方法建立LIRI大鼠模型。此外，我们建立了一种人肺动脉内皮细胞缺氧8小时，然后复氧16小时的细胞模型，以确定CYP 2 J2过表达和外源性11，12-EET的抗炎作用和机制。结果如下：肺缺血/再灌注增加了肺湿/干和肺重量/体重比、支气管肺泡灌洗液中的蛋白浓度和血清中促炎介质（包括IL-1 β、IL-8、TNF-α、sP-和sE-选择素）的浓度，并降低了抗炎介质IL-10的浓度。光镜下可见缺血/再灌注后肺水肿和炎症反应。缺血再灌注肺组织NF-κ B p65的活化和I-κ B α的降解明显增加。而CYP 2 J2过表达可显著抑制上述作用（p
Background: Injurious inflammatory response is critical to the development of lung ischemia/reperfusion injury (LIRI). The cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert an anti-inflammatory effect on the cardiovascular system. We therefore hypothesized that CYP2J2 overexpression and pretreatment with exogenous EETs may have the potential to reduce LIRI. Methods: A rat model was used to mimic the condition of LIRI by clamping the left pulmonary hilum for 60 minutes, followed by reperfusion for 2 hours. Moreover, we developed a cell model using human pulmonary artery endothelial cells by anoxia for 8 hours, followed by reoxygenation for 16 hours to determine the anti-inflammatory effect and mechanism of CYP2J2 overexpression and exogenous 11,12-EET. Results: Lung ischemia/reperfusion increased lung wet/dry and lung weight/body weight ratios, protein concentration in bronchoalveolar lavage fluid and concentrations of pro-inflammatory mediators in serum, including IL-1 beta, IL-8, TNF-alpha, sP- and sE-selectin, and decreased concentration of anti-inflammatory mediator IL-10. Ischemia/reperfusion also leaded to pulmonary edema and inflammation under light microscopy. Furthermore, activation of NF-kappa B p65 and degradation of I kappa B alpha were remarkably increased in ischemia/reperfusion lung tissues. While CYP2J2 overexpression significantly inhibited the above effects (p