Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Anesthesiology. 2011 Nov;115(5):1012-21. doi: 10.1097/ALN.0b013e31823306cf.
The antiinflammatory effects of hydrogen sulfide (H2S) and sodium sulfide (Na2S) treatment may prevent acute lung injury induced by high tidal volume (HVT) ventilation. However, lung protection may be limited by direct pulmonary toxicity associated with H2S inhalation. Therefore, the authors tested whether the inhalation of H2S or intravascular Na2S treatment can protect against ventilator-induced lung injury in mice.
Anesthetized mice continuously inhaled 0, 1, 5, or 60 ppm H2S or received a single bolus infusion of Na2S (0.55 mg/kg) or vehicle and were then subjected to HVT (40 ml/kg) ventilation lasting 4 h (n = 4-8 per group).
HVT ventilation increased the concentrations of protein and interleukin-6 in bronchoalveolar lavage fluid, contributing to reduced respiratory compliance and impaired arterial oxygenation, and caused death from lung injury and pulmonary edema. Inhalation of 1 or 5 ppm H2S during HVT ventilation did not alter lung injury, but inhalation of 60 ppm H2S accelerated the development of ventilator-induced lung injury and enhanced the pulmonary expression of the chemoattractant CXCL-2 and the leukocyte adhesion molecules CD11b and L-selectin. In contrast, pretreatment with Na2S attenuated the expression of CXCL-2 and CD11b during HVT ventilation and reduced pulmonary edema. Moreover, Na2S enhanced the pulmonary expression of Nrf2-dependent antioxidant genes (NQO1, GPX2, and GST-A4) and prevented oxidative stress-induced depletion of glutathione in lung tissue.
The data suggest that systemic intravascular treatment with Na2S represents a novel therapeutic strategy to prevent both ventilator-induced lung injury and pulmonary glutathione depletion by activating Nrf2-dependent antioxidant gene transcription.
硫化氢（H2S）和硫化钠（Na2S）的抗炎作用可能预防大潮气量（HVT）通气引起的急性肺损伤。然而，H2S 吸入相关的直接肺毒性可能会限制肺保护作用。因此，作者测试了 H2S 吸入或血管内 Na2S 治疗是否可以保护小鼠免受呼吸机诱导的肺损伤。
麻醉小鼠连续吸入 0、1、5 或 60 ppm H2S，或单次静脉推注 Na2S（0.55 mg/kg）或载体，然后进行 4 小时的 HVT（40 ml/kg）通气（每组 4-8 只）。
HVT 通气增加了支气管肺泡灌洗液中蛋白质和白细胞介素-6 的浓度，导致呼吸顺应性降低和动脉氧合受损，并导致肺损伤和肺水肿导致的死亡。HVT 通气期间吸入 1 或 5 ppm H2S 不会改变肺损伤，但吸入 60 ppm H2S 加速了呼吸机诱导的肺损伤的发展，并增强了趋化因子 CXCL-2 和白细胞黏附分子 CD11b 和 L-选择素的肺表达。相比之下，Na2S 预处理可减轻 HVT 通气过程中 CXCL-2 和 CD11b 的表达，并减少肺水肿。此外，Na2S 增强了 Nrf2 依赖性抗氧化基因（NQO1、GPX2 和 GST-A4）的肺表达，并防止氧化应激诱导的肺组织谷胱甘肽耗竭。
数据表明，系统血管内给予 Na2S 通过激活 Nrf2 依赖性抗氧化基因转录，代表了一种预防呼吸机诱导的肺损伤和肺组织谷胱甘肽耗竭的新治疗策略。
