Estradiol mediates the long-lasting lung inflammation induced by intestinal ischemia and reperfusion
Estradiol mediates the long-lasting lung inflammation induced by intestinal ischemia and reperfusion
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DOI：
10.1016/j.jss.2017.07.038
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发表时间：
2018-01-01
影响因子：
2.2
通讯作者：
Tavares-de-Lima, Wothan
中科院分区：
文献类型：
--
作者：
Fantozzi, Evelyn Thais;Breithaupt-Faloppa, Ana Cristina;Tavares-de-Lima, Wothan
背景：肺炎症是肠缺血再灌注的主要后果之一，严重者可导致急性呼吸窘迫综合征和死亡。我们先前已经证明雌二醇对雄性大鼠肠IR引起的肺水肿和细胞因子释放具有保护作用。材料和方法：在雌性大鼠肠IR模型中，观察雌二醇对IL-1β、IL-10、血管内皮生长因子(VEGF)和细胞因子诱导的中性粒细胞趋化因子-1(CINC-1)产生的影响。血液和骨髓白细胞也进行了定量。7天龄去卵巢大鼠结扎肠系膜上动脉造成肠缺血45min。再灌流2 h后处死大鼠。结果：血清IL-10、CINC-1、尿酸水平及外周血白细胞数均显著升高，但骨髓白细胞数无明显变化。此外，肠缺血诱导体外肺组织中IL-1β、IL-10和血管内皮生长因子水平显著升高。肠IR诱导前给予17b-雌二醇可阻止IL-10、CINC-1和尿酸的全身释放，但对白细胞增多无影响。此外，17b-雌二醇显著抑制肺组织IL-1b和VEGF的体外释放。结论：肠道IR干扰肺内环境的稳定，使肺组织在缺血后至少24小时产生促炎介质。此外，我们的数据证实，肠道IR引起的炎症反应是由雌二醇介导的。(C)2017 Elsevier Inc.保留所有权利。
Background: Lung inflammation is one of the main consequences of intestinal ischemia reperfusion (intestinal IR) and, in severe cases, can lead to acute respiratory distress syndrome and death. We have previously demonstrated that estradiol exerts a protective effect on lung edema and cytokine release caused by intestinal IR in male rats.Materials and methods: We investigated the role of estradiol on the generation of interleukin (IL)-1 beta, IL-10, vascular endothelial growth factor (VEGF), and cytokine-induced neutrophil chemoattractant 1 (CINC-1) in a female rat model of intestinal IR. Blood and bone marrow leukocytes were also quantified. Seven-days-ovariectomized rats were subjected to intestinal IR by occlusion of the superior mesenteric artery for 45 min. After reperfusion of the tissue for 2 h, the rats were sacrificed. Lung tissue was collected, cultured for 24 h and assayed.Results: We observed a significant increase in serum levels of IL-10, CINC-1, uric acid and circulating, but not bone marrow, leukocyte numbers. In addition, intestinal IR induced a significant increase in the ex-vivo lung levels of IL-1 beta, IL-10, and VEGF. Treatment with 17b-estradiol before the induction of intestinal IR prevented the systemic release of IL-10, CINC-1, and uric acid, but it did not affect the leukocytosis. In addition, 17b-estradiol significantly prevented the ex-vivo release of IL-1b and VEGF from lung tissue.Conclusions: We demonstrated that intestinal IR interferes with lung homeostasis, priming the tissue to generate proinflammatory mediators for at least 24 h postischemia. Furthermore, our data confirm that the inflammatory responses caused by intestinal IR are estradiol mediated. (C) 2017 Elsevier Inc. All rights reserved.