Protection by Inhaled Hydrogen Therapy in a Rat Model of Acute Lung Injury can be Tracked in vivo Using Molecular Imaging.
Protection by Inhaled Hydrogen Therapy in a Rat Model of Acute Lung Injury can be Tracked in vivo Using Molecular Imaging.
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DOI：
10.1097/shk.0000000000000872
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Clough AV
中科院分区：
文献类型：
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作者：
Audi SH;Jacobs ER;Zhang X;Camara AKS;Zhao M;Medhora MM;Rizzo B;Clough AV
吸入氢气 (H2) 可为人类急性肺损伤 (ALI) 大鼠模型提供保护。我们之前报道过生物标志物成像可以检测 ALI 大鼠模型体内的氧化应激和内皮细胞死亡。我们的目的是评估 99mTc-六甲基丙烯胺肟 (HMPAO) 和 99mTc-耐久霉素在 ALI 高氧大鼠模型中追踪体内 H2 疗法有效性的能力。大鼠暴露于室内空气（含氧量正常）、98% O2 + 2% N2（高氧）或 98% O2 + 2% H2（高氧+H2）长达 60 小时。注射 99mTc-HMPAO 或 99mTc-耐久霉素后获得体内闪烁扫描图像。对于高氧大鼠，99mTc-HMPAO 和 99mTc-耐久霉素肺吸收以时间依赖性方式增加，在 60 小时分别达到最大增加 270% 和 150%。在高氧+H2 大鼠中，这些增加分别降至 120% 和 70%。高氧暴露使肺匀浆中谷胱甘肽含量 (36%) 的增加多于高氧 + H2 (21%)，这与 99mTc-HMPAO 肺摄取测量的增加一致。在60小时高氧大鼠中，胸腔积液平均为9.3克/只，而在常氧大鼠中检测不到，并且肺组织3-硝基酪氨酸表达增加了790%。在 60 小时高氧+H2 大鼠中，增加值分别减少了 69% 和 59%。这项研究检测并追踪了 H2 疗法在高氧暴露 24 小时后体内的抗氧化和抗凋亡特性。结果表明，这些 SPECT 生物标记物可用于体内评估 ALI 发病机制中的关键细胞通路以及监测治疗反应。
Inhaled hydrogen gas (H2) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of 99mTc-hexamethylpropyleneamineoxime (HMPAO) and 99mTc-duramycin to track the effectiveness of H2 therapy in vivo in the hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O2 + 2% N2 (hyperoxia) or 98% O2 + 2% H2 (hyperoxia+H2) for up to 60 hrs. In vivo scintigraphy images were acquired following injection of 99mTc-HMPAO or 99mTc-duramycin. For hyperoxia rats, 99mTc-HMPAO and 99mTc-duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 hrs, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxia+H2 rats. Hyperoxia exposure increased glutathione content in lung homogenate (36%) more than hyperoxia+H2 (21%), consistent with increases measured in 99mTc-HMPAO lung uptake. In 60-hr hyperoxia rats, pleural effusion, which was undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue 3-nitrotyrosine expression increased by 790%. Increases were reduced by 69% and 59%, respectively, in 60-hr hyperoxia+H2 rats. This study detects and tracks the anti-oxidant and anti-apoptotic properties of H2 therapy in vivo after as early as 24 hrs of hyperoxia exposure. The results suggest the potential utility of these SPECT biomarkers for in vivo assessment of key cellular pathways in the pathogenesis of ALI and for monitoring responses to therapies.