Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury
Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury
复制标题
DOI：
10.1152/jappl.1998.85.5.1753
复制
发表时间：
1998-11-01
影响因子：
3.3
通讯作者：
Tucker, A
中科院分区：
文献类型：
--
作者：
Parker, JC;Ivey, CL;Tucker, A
我们确定调节蛋白质酪氨酸磷酸化状态的药物是否可以改变离体灌注大鼠肺中高气道压力诱导的微血管损伤的阈值。肺连续通气 30 分钟，峰值充气压力 (PIP) 为 7、20、30 和 35 cmH(2)O，然后测量毛细血管滤过系数 (K-fc)，这是水力传导的敏感指数。在未经治疗的对照肺中，用 30 和 35 cmH(2)O PIP 通气后，K-fc 相对于基线 (7 cmH(2)O PIP) 增加了 1.3 和 3.3 倍。然而，在用 100 μM 氧化苯胂（一种磷酸酪氨酸磷酸酶抑制剂）处理的肺部中，在这些 PIP 值下，K-fc 相对于基线增加了 4.7 倍和 16.4 倍。在用50μM金雀异黄素（一种酪氨酸激酶抑制剂）处理的肺中，K-fc仅在35cmH(2)O PIP时显着增加，并且三组之间存在显着差异。因此，磷酸酪氨酸磷酸酶抑制增加了大鼠肺对高PIP损伤的敏感性，而酪氨酸激酶抑制相对于高PIP对照肺减轻了损伤。
We determined whether drugs which modulate the state of protein tyrosine phosphorylation could alter the threshold for high airway pressure-induced microvascular injury in isolated perfused rat lungs. Lungs were ventilated for successive 30-min periods with peak inflation pressures (PIP) of 7, 20, 30, and 35 cmH(2)O followed by measurement of the capillary filtration coefficient (K-fc), a sensitive index of hydraulic conductance. In untreated control lungs, K-fc increased by 1.3- and 3.3-fold relative to baseline (7 cmH(2)O PIP) after ventilation with 30 and 35 cmH(2)O PIP. However, in lungs treated with 100 mu M phenylarsine oxide (a phosphotyrosine phosphatase inhibitor), K-fc increased by 4.7- and 16.4-fold relative to baseline at these PIP values. In lungs treated with 50 mu M genistein (a tyrosine kinase inhibitor), K-fc increased significantly only at 35 cmH(2)O PIP, and the three groups were significantly different from each other. Thus phosphotyrosine phosphatase inhibition increased the susceptibility of rat lungs to high-PIP injury, and tyrosine kinase inhibition attenuated the injury relative to the high-PIP control lungs.