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首页> 外文期刊>American Journal of Physiology >Protective effect of purinergic agonist ATP7S against acute lung injury
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Protective effect of purinergic agonist ATP7S against acute lung injury

机译：嘌呤能激动剂ATP7S对急性肺损伤的保护作用

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First published November 9, 2007; doi:10.1152/ajplung.00283.2007.-Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of acute respiratory failure associated with high morbidity and mortality. Although ALI/ARDS pathogenesis is only partly understood, pulmonary endothelium plays a major role by regulating lung fluid balance and pulmonary edema formation. Consequently, endothelium-targeted therapies may have beneficial effects in ALI/ARDS. Recently, attention has been given to the therapeutic potential of purinergic agonists and antagonists for the treatment of cardiovascular and pulmonary diseases. Extracellular purines (adenosine, ADP, and ATP) and pyri-midines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface P2Y receptors. We previously described ATP-induced endothelial cell (EC) barrier enhancement via a complex cell signaling and hypothesized endothelial purinoreceptors activation to exert anti-inflammatory barrier-protective effects. To test this hypothesis, we used a murine model of ALI induced by intratracheal administration of endotoxin/lipopolysaccha-ride (LPS) and cultured pulmonary EC. The nonhydrolyzed ATP analog ATP7S (50~(-1)00 muM final blood concentration) attenuated inflammatory response with decreased accumulation of cells (48%, P < 0.01) and proteins (57%, P < 0.01) in bronchoalveolar lavage and reduced neutrophil infiltration and extravasation of Evans blue albumin dye into lung tissue. In cell culture model, ATP7S inhibited junctional permeability induced by LPS. These findings suggest that purinergic receptor stimulation exerts a protective role against ALI by preserving integrity of endothelial cell-cell junctions.
机译：首次发布于2007年11月9日; doi：10.1152 / ajplung.00283.2007.-急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是与高发病率和高死亡率相关的急性呼吸衰竭的主要原因。尽管仅部分了解ALI / ARDS的发病机理，但肺内皮通过调节肺液平衡和肺水肿形成起着重要作用。因此，靶向内皮的疗法可能在ALI / ARDS中具有有益的作用。最近，人们已经注意到嘌呤能激动剂和拮抗剂在治疗心血管和肺部疾病方面的治疗潜力。细胞外嘌呤（腺苷，ADP和ATP）和嘧啶（UDP和UTP）是重要的信号分子，它们通过细胞表面P2Y受体介导多种生物学作用。我们先前描述了通过复杂的细胞信号传导和假定的内皮嘌呤受体激活作用来发挥抗炎性屏障保护作用的ATP诱导的内皮细胞（EC）屏障增强。为了验证该假设，我们使用了通过气管内施用内毒素/脂多糖（LPS）和培养的肺EC诱导的ALI小鼠模型。未水解的ATP类似物ATP7S（终浓度为50〜（-1）00μM）减轻了炎症反应，支气管肺泡灌洗液中的细胞（48％，P <0.01）和蛋白质（57％，P <0.01）积累减少，中性粒细胞减少Evans蓝白蛋白染料向肺组织的浸润和渗出。在细胞培养模型中，ATP7S抑制LPS诱导的连接通透性。这些发现表明嘌呤能受体刺激通过保持内皮细胞-细胞连接的完整性而对ALI起保护作用。

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