Mechanotransduction in the lung -: Ventilation-induced lung injury and mechanotransduction:: stretching it too far?
Mechanotransduction in the lung -: Ventilation-induced lung injury and mechanotransduction:: stretching it too far?
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DOI：
10.1152/ajplung.00124.2001
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发表时间：
2002-05-01
影响因子：
4.9
通讯作者：
Uhlig, S
中科院分区：
文献类型：
--
作者：
Uhlig, S
急性呼吸窘迫综合征网络对危重患者通气的临床试验引起了人们对机械通气潜在副作用的关注。临床和基础研究都表明，有害的通气策略可以引发或延续局部和全身炎症反应。产生这种反应的主要机制有四种。1)通气，特别是高通气压力和零呼气末正压通气，可引起质膜和上皮和内皮屏障的应激衰竭。质膜的应激失败导致坏死，这导致预先形成的炎症介质和刺激其他完整细胞产生这些介质的介质的释放。2)应激障碍的失效导致区隔丧失，从而导致介质和细菌在全身扩散。3)不引起组织破坏的伤害较小的通气策略可以通过更具体的机制引发介质的释放，可能是通过激活拉伸激活的信号级联（机械转导）。4)正压增加的通气会增加肺循环压力，从而增加血管剪切应力，这两者都是已知的内皮细胞刺激。在设计和解释通气所致肺损伤的分子机制时，应考虑到这些不同的机制。
The Acute Respiratory Distress Syndrome Network clinical trial on ventilation of critically ill patients has drawn attention to the potential side effects of mechanical ventilation. Both clinical and basic research have demonstrated that injurious ventilation strategies can initiate or perpetuate local and systemic inflammatory responses. There are four principal mechanisms that can produce such a response. 1) Ventilation, especially with high ventilation pressures and zero positive end-expiratory pressure, can cause stress failure of the plasma membrane and of epithelial and endothelial barriers. Stress failure of the plasma membrane causes necrosis, which leads to liberation of both preformed inflammatory mediators and agents that stimulate other cells that are still intact to produce such mediators. 2) Stress failure of the barriers causes loss of compartmentalization with spread of mediators and bacteria throughout the body as a consequence. 3) Less injurious ventilation strategies that do not cause tissue destruction can elicit release of mediators by more specific mechanisms, presumably through activation of stretch-activated signaling cascades (mechanotransduction). 4) Ventilation with increasing positive pressures raises the pressure in the pulmonary circulation and thus vascular shear stress, both of which are known stimuli for endothelial cells. These different mechanisms should be taken into account in the design and the interpretation of studies on molecular mechanisms of ventilation-induced lung injury.