Na,K-ATPase gene transfer during ventilation-induced increases liquid clearance lung injury
Na,K-ATPase gene transfer during ventilation-induced increases liquid clearance lung injury
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DOI：
10.1164/rccm.200207-702oc
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发表时间：
2003-12-15
影响因子：
24.7
通讯作者：
Sznajder, JI
中科院分区：
文献类型：
--
作者：
Adir, Y;Factor, P;Sznajder, JI
高潮气量 (HVT) 机械通气会下调肺泡 Na,K-ATP 酶功能并损害肺液体清除率。我们假设肺泡上皮中 Na,K-ATP 酶的过度表达可以抵消这些变化并增加轻度通气引起的肺损伤大鼠模型的清除率。我们使用基于表面活性剂的系统，在通气前 7 天，将 4 X 10(9) 个空斑形成单位的 E1 a(-)/E3(-) 重组腺病毒（含有大鼠 beta(1) Na,KATPase 亚基 cDNA (adbeta(1)) 或不含 cDNA (adnull)）递送至大鼠肺部，V-T 约为 40 ml/kg（峰值气道压力小于 35 厘米水柱）40 分钟。与假手术和adnull感染的HVT肺相比，HVT adbeta(1)感染的肺的肺液体清除率以及Na、K-ATP酶活性和蛋白质丰度增加。这些结果表明，肺泡上皮中 Na,K-ATP 酶亚基基因的过度表达会增加 HVT 模型中 Na,K-ATP 酶的功能和肺液体清除率。我们在这里提供了第一个证据，证明使用遗传方法可以改善活性 Na+ 转运，从而改善轻度通气引起的肺损伤时的液体清除。
Mechanical ventilation with high tidal volumes (HVT) downregulates alveolar Na,K-ATPase function and impairs lung liquid clearance. We hypothesized that overexpression of Na,K-ATPase in the alveolar epithelium could counterbalance these changes and increase clearance in a rat model of mild ventilation-induced lung injury. We used a surfactant-based system to deliver 4 X 10(9) plaque-forming units of E1 a(-)/E3(-) recombinant adenovirus containing either a rat beta(1) Na,KATPase subunit cDNA (adbeta(1)) or no cDNA (adnull) to rat lungs 7 days before ventilation with a V-T of approximately 40 ml/kg (peak airway pressure of less than 35 cm H2O) for 40 minutes. Lung liquid clearance and Na, K-ATPase activity and protein abundance were increased in HVT adbeta(1)-infected lungs as compared with sham and adnull-infected HVT lungs. These results suggest that Na,K-ATPase subunit gene overexpression in the alveolar epithelium increases Na,K-ATPase function and lung liquid clearance in a model of HVT. We provide here the first evidence that using a genetic approach improves active Na+ transport and thus liquid clearance in the setting of mild ventilation-induced lung injury.