Genetic targets of hydrogen sulfide in ventilator-induced lung injury

In this study we provide evidence on potential mechanisms involved in H2S mediated protection against VILI. H2S down-regulates genes that are involved in oxidative stress and pro-inflammatory cell responses. H2S regulates ECM remodelling, a mechanism which may contribute to H2S-mediated lung protection. In addition, H2S inhalation activates anti-apoptotic and anti-inflammatory genes, and genes controlling the vascular permeability. The functional relevance of Atf3 underscores the potential of H2S to limit lung injury. We utilized a microarray approach for large scale analysis of target genes in order to elucidate the therapeutic effects of H2S in VILI. This study demonstrates the influence of supplemental H2S on gene expression in a model of VILI. In addition to describing the genes differentially regulated in VILI, the present study focused on newly identified H2S target genes within several functional groups, including anti-inflammatory and anti-apoptotic pathways, regulation of extracellular matrix (ECM) remodelling and angiogenesis. Gene expression analysis of control group, allowed to breathe spontaneously synthetic air and mice ventilated with synthetic air or synthetic air with 80 ppm H2S for 6 hours.

本研究旨在为硫化氢（H2S）介导的呼吸机相关性肺损伤（VILI, Ventilator-Induced Lung Injury）保护作用的潜在机制提供实验证据。硫化氢可下调参与氧化应激与促炎症细胞应答的基因表达，还可调控细胞外基质（ECM, Extracellular Matrix）重塑，这一机制或有助于硫化氢介导的肺保护作用。此外，吸入硫化氢可激活抗凋亡、抗炎基因以及调控血管通透性的相关基因。激活转录因子3（Atf3, Activating Transcription Factor 3）的功能相关性进一步凸显了硫化氢限制肺损伤的应用潜力。为阐明硫化氢在呼吸机相关性肺损伤中的治疗作用，本研究采用基因芯片技术对靶基因进行大规模分析，明确了外源性补充硫化氢对呼吸机相关性肺损伤模型中基因表达的调控作用。除了阐明呼吸机相关性肺损伤中差异表达的基因外，本研究还重点分析了多个功能类群中新发现的硫化氢靶基因，涵盖抗炎与抗凋亡通路、细胞外基质（ECM）重塑调控以及血管生成等方向。本研究对实验小鼠开展了基因表达分析，其中对照组小鼠可自主呼吸合成空气，其余小鼠分别以合成空气、含80ppm硫化氢的合成空气进行6小时机械通气。