Protective and Detrimental Effects of Sodium Sulfide and Hydrogen Sulfide in Murine Ventilator-induced Lung Injury.
Protective and Detrimental Effects of Sodium Sulfide and Hydrogen Sulfide in Murine Ventilator-induced Lung Injury.
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DOI：
10.1097/aln.0b013e31823306cf
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发表时间：
2011-11
期刊：
影响因子：
8.8
通讯作者：
Zapol WM
中科院分区：
文献类型：
--
作者：
Francis RC;Vaporidi K;Bloch KD;Ichinose F;Zapol WM
硫化氢（H2S）和硫化钠（Na2S）治疗的抗炎作用可以预防高潮气量（HVT）通气引起的急性肺损伤。然而，肺保护可能会受到与吸入 H2S 相关的直接肺部毒性的限制。因此，作者测试了吸入 H2S 或血管内 Na2S 治疗是否可以预防小鼠呼吸机引起的肺损伤。麻醉小鼠连续吸入 0、1、5 或 60 ppm H2S 或接受单次推注 Na2S (0.55 mg/kg) 或载体，然后进行持续 4 小时的 HVT (40 ml/kg) 通气（每组 n = 4-8）。 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 会加速呼吸机引起的肺损伤的发展，并增强化学引诱剂 CXCL-2 以及白细胞粘附分子 CD11b 和 L-选择素的肺部表达。相反，Na2S 预处理减弱了 HVT 通气期间 CXCL-2 和 CD11b 的表达，并减少了肺水肿。此外，Na2S 增强了 Nrf2 依赖性抗氧化基因（NQO1、GPX2 和 GST-A4）的肺部表达，并防止氧化应激诱导的肺组织中谷胱甘肽的消耗。数据表明，Na2S 全身血管内治疗代表了一种新的治疗策略，通过激活 Nrf2 依赖性抗氧化基因转录来预防呼吸机引起的肺损伤和肺谷胱甘肽耗竭。
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.