Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells
Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells
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DOI：
10.1152/ajplung.00069.2005
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发表时间：
2005-11-01
影响因子：
4.9
通讯作者：
Waters, CM
中科院分区：
文献类型：
--
作者：
Chapman, KE;Sinclair, SE;Waters, CM
机械通气期间肺组织过度膨胀可能是引发呼吸机相关性肺损伤（VILI）的因素之一。我们假设肺上皮的循环机械拉伸 (CMS) 通过产生活性氧 (ROS) 参与 VILI 的早期事件。对永生化人气道上皮细胞系（16HBE）、人肺泡II型细胞系（A549）的培养物和大鼠肺泡II型细胞的原代培养物进行循环拉伸，并通过二氢乙锭荧光测量超氧化物（O-2（-））的产生。 2 小时后，CMS 刺激每种类型细胞中 O-2(-) 的产生增加。 16HBE 细胞在 CMS 2 小时（20% 应变，30 个循环/分钟）之前没有表现出明显的 ROS 刺激，并且 24 小时后 ROS 产生恢复到控制水平。谷胱甘肽 (GSH)（一种细胞抗氧化剂）的氧化随着 CMS 的增加而增加，通过还原 GSH 水平与氧化 GSH 水平之比的降低来衡量。 10% 的菌株水平不会增加 16HBE 细胞中 O-2(-) 的产生，而 15%、20% 和 30% 的菌株水平会显着增加 O-2(-) 的产生。鱼藤酮 (Rotenone) 是一种线粒体复合物 I 抑制剂，在 16HBE 细胞中 2 小时 CMS 后，部分消除了拉伸诱导的 O-2(-) 生成。 CMS 2 小时后 NADPH 氧化酶活性增加，有助于 O-2(-) 的产生。肺上皮细胞因拉伸增加而产生的 ROS 增加可能导致 VILI 的发生。
Overdistention of lung tissue during mechanical ventilation may be one of the factors that initiates ventilator-induced lung injury (VILI). We hypothesized that cyclic mechanical stretch (CMS) of the lung epithelium is involved in the early events of VILI through the production of reactive oxygen species ( ROS). Cultures of an immortalized human airway epithelial cell line (16HBE), a human alveolar type II cell line (A549), and primary cultures of rat alveolar type II cells were cyclically stretched, and the production of superoxide (O-2(-)) was measured by dihydroethidium fluorescence. CMS stimulated increased production of O-2(-) after 2 h in each type of cell. 16HBE cells exhibited no significant stimulation of ROS before 2 h of CMS ( 20% strain, 30 cycles/min), and ROS production returned to control levels after 24 h. Oxidation of glutathione (GSH), a cellular antioxidant, increased with CMS as measured by a decrease in the ratio of the reduced GSH level to the oxidized GSH level. Strain levels of 10% did not increase O-2(-) production in 16HBE cells, whereas 15, 20, and 30% significantly increased generation of O-2(-). Rotenone, a mitochondrial complex I inhibitor, partially abrogated the stretch-induced generation of O-2(-) after 2 h CMS in 16HBE cells. NADPH oxidase activity was increased after 2 h of CMS, contributing to the production of O-2(-). Increased ROS production in lung epithelial cells in response to elevated stretch may contribute to the onset of VILI.