Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB dependent mechanism
Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB dependent mechanism
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DOI：
10.1097/ccm.0b013e318258f8b4
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发表时间：
2012-09-01
影响因子：
8.8
通讯作者：
Laffey, John G.
中科院分区：
文献类型：
--
作者：
Contreras, Maya;Ansari, Bilal;Laffey, John G.
目的：高碳酸血症可预防通气引起的肺损伤。我们希望确定高碳酸血症酸中毒在减少牵张引起的损伤方面的有益作用是否是通过抑制核因子-κ B（炎症、损伤和修复中的关键转录调节因子）介导的。设计：前瞻性随机动物研究。环境：大学研究实验室。受试者：成年雄性 Sprague-Dawley 大鼠。干预措施：在单独的实验系列中，确定了高碳酸血症酸中毒减轻中度和重度通气引起的肺损伤的潜力。在每个系列中，在诱导麻醉和气管造口术后，将 Sprague-Dawley 大鼠随机分为（正常碳酸血症；Fico(2) 0.00）或（高碳酸血症；Fico(2) 0.05），接受高牵张通气，并评估肺损伤的严重程度和核因子-κ B 通路的激活指数。随后的体外实验检查了高碳酸血症酸中毒减少循环机械拉伸引起的肺上皮炎症和损伤的潜力。然后确定了核因子-κ B 通路在高碳酸酸中毒介导的拉伸损伤保护中的作用。测量和主要结果：与正常碳酸血症条件相比，高碳酸酸中毒可减轻中度和重度通气引起的肺损伤，这可以通过改善氧合、顺应性和减少组织学损伤来证明。高碳酸血症酸中毒降低了炎症指标，例如白细胞介素6和支气管肺泡灌洗中性粒细胞浸润。高碳酸血症降低了核因子-κ B 抑制剂 I kappa B α 的减少，并减少了细胞因子诱导的中性粒细胞趋化剂-1 的产生。与正常碳酸血症相比，高碳酸血症酸中毒可减少周期性机械牵张诱导的核因子 kappa B 激活，减少白细胞介素 8 的产生，并减少上皮损伤和细胞死亡。结论：高碳酸血症酸中毒可通过核因子 kappa B 依赖性机制减轻通气引起的肺损伤，且与损伤严重程度无关，并减少机械牵张诱导的上皮损伤和死亡。 （《重症监护医学》2012 年；40：2622-2630）
Objectives: Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-kappa B, a key transcriptional regulator in inflammation, injury, and repair.Design: Prospective randomized animal study.Setting: University research laboratory.Subjects: Adult male Sprague-Dawley rats.Interventions: In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; Fico(2) 0.00) or (hypercapnic acidosis; Fico(2) 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-kappa B pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-kappa B pathway in hypercapnic acidosis mediated protection from stretch injury was then determined.Measurements and Main Results: Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-kappa B inhibitor I kappa B alpha and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-kappa B activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia.Conclusions: Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-kappa B dependent mechanism. (Crit Care Med 2012; 40:2622-2630)