In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury
In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury
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DOI：
10.1136/thx.2007.080382
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发表时间：
2008-03-01
期刊：
影响因子：
10
通讯作者：
Thickett, D. R.
中科院分区：
文献类型：
--
作者：
Perkins, G. D.;Gao, F.;Thickett, D. R.
背景：急性肺损伤是危重病人呼吸衰竭的重要原因。它是由肺泡屏障受损引起的，随后的肺泡淹没导致难治性低氧血症的发展。β激动剂刺激肺损伤动物模型中的肺泡液清除。在一项临床试验（巴尔蒂-1）中，静脉注射β受体激动剂可减少血管外肺水，与动物研究结果相反，该作用持续72小时。一个可能的解释是延迟在血管外肺水的变化是沙丁胺醇刺激肺泡上皮repair.Objective所需的时间：探讨是否沙丁胺醇可以刺激肺泡上皮repairinvivo and in vitro.Results：静脉注射沙丁胺醇减少急性呼吸窘迫综合征（ARDS）患者的肺泡毛细血管通透性的措施。在体外，沙丁胺醇刺激伤口修复，A549细胞和远端肺上皮细胞的扩散和增殖。与安慰剂治疗的患者相比，沙丁胺醇治疗的患者肺灌洗液增强伤口修复反应，在体外由白细胞介素1 β依赖mechanism.Conclusions：我们在体内和体外的工作表明，沙丁胺醇可能刺激上皮修复潜在的药理学第一次在ARDS。清楚地建立机制和途径负责这是重要的未来，并可能允许识别新的治疗靶点，以促进肺泡上皮修复的人与ARDS。
Background: Acute lung injury is an important cause of respiratory failure in the critically ill patient. It is caused by damage to the alveolar barrier with subsequent alveolar flooding leading to the development of refractory hypoxaemia. beta Agonists stimulate alveolar fluid clearance in animal models of lung injury. In a clinical trial (BALTI-1), intravenous beta agonists reduced extravascular lung water, an effect that took 72 h in contrast with what animal studies suggest. One possible explanation for the delay in change in extravascular lung water is the time required for salbutamol to stimulate alveolar epithelial repair.Objective: To investigate whether salbutamol can stimulate alveolar epithelial repair in vivo and in vitro.Results: Intravenous salbutamol reduced measures of alveolar-capillary permeability in patients with acute respiratory distress syndrome (ARDS). In vitro, salbutamol stimulated both wound repair, and spreading and proliferation of A549 cells and distal lung epithelial cells. Lung lavage fluid from patients treated with salbutamol enhanced wound repair responses compared with placebo treated patients in vitro by an interleukin 1 beta dependent mechanism.Conclusions: Our in vivo and in vitro work suggests that salbutamol may stimulate epithelial repair-potentially a pharmacological first in ARDS. Clearly establishing the mechanisms and pathways responsible for this is important for the future, and may allow identification of novel therapeutic targets to promote alveolar epithelial repair in humans with ARDS.