Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study
Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study
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DOI：
10.1186/1465-9921-9-79
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发表时间：
2008-12-13
影响因子：
5.8
通讯作者：
Hashimoto, Satoru
中科院分区：
文献类型：
--
作者：
Matsuyama, Hiroki;Amaya, Fumimasa;Hashimoto, Satoru
背景资料：细胞外三磷酸腺苷（ATP）是一种内源性信号分子，参与多种生物学现象，包括炎症。细胞外ATP在肺中的作用尚未完全阐明。本研究探讨1）细胞外ATP在肺部炎症发病机制中的生物学作用和2）细胞外ATP参与机械通气诱导的肺损伤的可能性。方法：通过测量肺湿干重比和肺渗透性指数来评估肺内ATP对肺渗透性、水肿或肺部炎症的影响，免疫组化和关键细胞因子的表达通过实时聚合酶链反应。采用荧光素酶法测定机械通气小鼠支气管肺泡灌洗液（BAL）中ATP浓度。结果：ATP主要通过ATP-P2 Y受体系统诱导肺内炎症反应，而P2 Y受体拮抗剂对肺内炎症反应有抑制作用。这些反应可通过与特异性P2受体拮抗剂共同给药而缓解。大潮气量机械通气引起肺部炎症，并增加BAL液中ATP浓度。P2受体拮抗剂部分减轻了大潮气量通气的炎症反应。结论：我们的观察表明，ATP-P2 Y受体系统部分参与了呼吸机所致肺损伤的发病机制。
Background: Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury.Methods: The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined.Results: ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation.Conclusion: Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.