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首页> 外文期刊>Critical care : >Cyclic arginine-glycine-aspartate attenuates acute lung injury in mice after intestinal ischemia/reperfusion
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Cyclic arginine-glycine-aspartate attenuates acute lung injury in mice after intestinal ischemia/reperfusion

机译：循环精氨酸-甘氨酸-天冬氨酸减轻肠道缺血/再灌注后小鼠的急性肺损伤

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IntroductionIntestinal ischemia is a critical problem resulting in multiple organ failure and high mortality of 60 to 80%. Acute lung injury (ALI) is a common complication after intestinal ischemia/reperfusion (I/R) injuries and contributes to the high mortality rate. Moreover, activated neutrophil infiltration into the lungs is known to play a significant role in the progression of ALI. Integrin-mediated interaction is involved in neutrophil transmigration. Synthetic peptides containing an arginine-glycine-aspartate sequence compete with adhesive proteins and inhibit integrin-mediated interaction and signaling. Thus, we hypothesized that the administration of a cyclic arginine-glycine-aspartate peptide (cRGD) inhibited neutrophil infiltration and provided protection against ALI induced by intestinal I/R.MethodsIschemia in adult male C57BL/6 mice was induced by fastening the superior mesenteric artery with 4-0 suture. Forty-five minutes later, the vascular suture was released to allow reperfusion. cRGD (5 mg/kg body weight) or normal saline (vehicle) was administered by intraperitoneal injection 1 hour prior to ischemia. Blood, gut, and lung tissues were collected 4 hours after reperfusion for various measurements.ResultsIntestinal I/R caused severe widespread injury to the gut and lungs. Treatment with cRGD improved the integrity of microscopic structures in the gut and lungs, as judged by histological examination. Intestinal I/R induced the expression of β1, β2 and β3 integrins, intercellular adhesion molecule-1, and fibronectin. cRGD significantly inhibited myeloperoxidase activity in the gut and lungs, as well as neutrophils and macrophages infiltrating the lungs. cRGD reduced the levels of TNF-α and IL-6 in serum, in addition to IL-6 and macrophage inflammatory protein-2 in the gut and lungs. Furthermore, the number of TUNEL-staining cells and levels of cleaved caspase-3 in the lungs were significantly lowered in the cRGD-treated mice in comparison with the vehicle mice.ConclusionsTreatment with cRGD effectively protected ALI and gut injury, lowered neutrophil infiltration, suppressed inflammation, and inhibited lung apoptosis after intestinal I/R. Thus, there is potential for developing cRGD as a treatment for patients suffering from ALI caused by intestinal I/R.
机译：简介肠缺血是导致多器官衰竭和60％至80％的高死亡率的关键问题。急性肺损伤（ALI）是肠缺血/再灌注（I / R）损伤后的常见并发症，并导致高死亡率。而且，已知活化的中性粒细胞浸润进入肺在ALI的进展中起重要作用。整联蛋白介导的相互作用参与嗜中性粒细胞的迁移。含有精氨酸-甘氨酸-天冬氨酸序列的合成肽与粘附蛋白竞争并抑制整联蛋白介导的相互作用和信号传导。因此，我们假设给予环精氨酸-甘氨酸-天冬氨酸肽（cRGD）可以抑制中性粒细胞浸润并提供针对肠I / R诱导的ALI的保护。方法通过系紧肠系膜上动脉诱导成年雄性C57BL / 6小鼠缺血4-0缝合。四十五分钟后，松开血管缝合线以进行再灌注。缺血前1小时腹膜内注射cRGD（5 mg / kg体重）或生理盐水（载体）。再灌注后4小时收集血液，肠和肺组织进行各种测量。结果肠I / R严重损害了肠和肺。根据组织学检查判断，cRGD治疗改善了肠道和肺部微观结构的完整性。肠I / R诱导了β1，β2和β3整联蛋白，细胞间粘附分子-1和纤连蛋白的表达。 cRGD显着抑制肠和肺以及浸润肺的嗜中性粒细胞和巨噬细胞的髓过氧化物酶活性。除了肠道和肺中的IL-6和巨噬细胞炎性蛋白2外，cRGD还降低了血清中TNF-α和IL-6的水平。此外，与媒介物小鼠相比，cRGD处理的小鼠中TUNEL染色细胞的数量和肺中caspase-3的裂解水平明显降低。肠I / R后炎症，并抑制肺细胞凋亡。因此，有可能开发出cRGD来治疗由肠I / R引起的ALI患者。

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