Specialized Proresolving Lipid Meditators Agonistic to Formyl Peptide Receptor Type 2 Attenuate Ischemia-reperfusion Injury in Rat Lung
Specialized Proresolving Lipid Meditators Agonistic to Formyl Peptide Receptor Type 2 Attenuate Ischemia-reperfusion Injury in Rat Lung
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DOI：
10.1097/tp.0000000000003987
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发表时间：
2021-11
期刊：
影响因子：
6.2
通讯作者：
H. Oda;S. Tanaka;M. Shinohara;Y. Morimura;Y. Yokoyama;H. Kayawake;Yoshito Yamada;Y. Yutaka;A. Ohsumi;D. Nakajima;M. Hamaji;T. Menju;H. Date
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文献类型：
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作者：
H. Oda;S. Tanaka;M. Shinohara;Y. Morimura;Y. Yokoyama;H. Kayawake;Yoshito Yamada;Y. Yutaka;A. Ohsumi;D. Nakajima;M. Hamaji;T. Menju;H. Date
背景肺缺血-再灌注损伤（IRI）是一种急性肺损伤，其特征在于由于强烈炎症引起的非特异性肺泡损伤和肺水肿。目前对肺IRI中特异性促分解脂质介质（SPMs）的作用知之甚少。因此，我们的目的是评估内源性SPM在肺IRI的开始和消退过程中的动态变化，并确定SPM补充对肺IRI的影响。方法.我们使用大鼠左肺门钳夹模型，缺血90分钟，然后再灌注。采用液相色谱-串联质谱法评价内源性SPM的动态变化。结果再灌注1h后，左肺内源性SPMs呈下降趋势。再灌注后3至7天，氧合有所改善;然而，与未处理肺相比，内源性SPM水平仍然较低。在SPM受体中，只有甲酰基肽受体2型（ALX/FPR 2）在左肺的基因表达增加3小时后再灌注，和炎症细胞的ALX/FPR 2的免疫化学阳性。阿司匹林触发（AT）消退素D1（AT-RvD 1）和AT脂氧素A4（AT-LXA 4），这是激动ALX/FPR 2，再灌注后立即管理改善肺功能，降低炎症细胞因子水平，减轻肺水肿，并减少中性粒细胞浸润后3小时再灌注。AT-RvD 1和AT-LXA 4在ALX/FPR 2拮抗剂预处理后未观察到作用。结论.在肺IRI过程中，肺内内源性SPMs水平降低，AT-RvD 1和AT-LXA 4给药可防止ALX/FPR 2引起的肺损伤加重。
Background. Lung ischemia-reperfusion injury (IRI) is a form of acute lung injury characterized by nonspecific alveolar damage and lung edema due to robust inflammation. Little is known about the roles of specialized proresolving lipid mediators (SPMs) in lung IRI. Therefore, we aimed to evaluate the dynamic changes in endogenous SPMs during the initiation and resolution of lung IRI and to determine the effects of SPM supplementation on lung IRI. Methods. We used a rat left hilar clamp model with 90 min of ischemia, followed by reperfusion. Dynamic changes in endogenous SPMs were evaluated using liquid chromatography-tandem mass spectrometry. Results. Endogenous SPMs in the left lung showed a decreasing trend after 1 h of reperfusion. Oxygenation improved between 3 and 7 d following reperfusion; however, the level of endogenous SPMs remained low compared with that in the naïve lung. Among SPM receptors, only formyl peptide receptor type 2 (ALX/FPR2) gene expression in the left lung was increased 3 h after reperfusion, and the inflammatory cells were immunohistochemically positive for ALX/FPR2. Administration of aspirin-triggered (AT) resolvin D1 (AT-RvD1) and AT lipoxin A4 (AT-LXA4), which are agonistic to ALX/FPR2, immediately after reperfusion improved lung function, reduced inflammatory cytokine levels, attenuated lung edema, and decreased neutrophil infiltration 3 h after reperfusion. The effects of AT-RvD1 and AT-LXA4 were not observed after pretreatment with the ALX/FPR2 antagonist. Conclusions. The level of intrapulmonary endogenous SPMs decreased during lung IRI process and the administration of AT-RvD1 and AT-LXA4 prevented the exacerbation of lung injury via ALX/FPR2.