99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment.
99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment.
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DOI：
10.1097/shk.0000000000000605
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Jacobs ER
中科院分区：
文献类型：
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作者：
Audi SH;Clough AV;Haworth ST;Medhora M;Ranji M;Densmore JC;Jacobs ER
99mTc-六亚甲基丙胺肟(HMPAO)是一种临床应用的组织氧化还原状态的单光子发射计算机断层扫描生物标志物。我们的目的是研究在两种已建立的人类急性肺损伤(ALI)大鼠模型中，HMPAO肺摄取是否可以作为肺损伤的临床前标志。大鼠暴露于95%O2(高氧)或气管内注射脂多糖(LPS)，24小时后获得第一个终点。在谷胱甘肽排泄剂马来酸二乙酯(DEM)治疗前和治疗后静脉注射HMPAO，采集核素图像，并从图像中定量HMPAO肺摄取。我们还测量了呼吸频率、心率、血氧饱和度、支气管肺泡灌洗(BAL)细胞计数和蛋白、肺组织匀浆谷胱甘肽(GSH)含量和肺血管内皮细胞过滤系数(KF)。对于高氧大鼠，暴露24小时(134%)和48小时(172%)后HMPAO肺摄取增加。内毒素处理组大鼠伤后24小时HMPAO肺摄取增加(188%)，随伤后消退而下降。与正常氧大鼠相比，DEM降低高氧和脂多糖大鼠HMPAO摄取的比例更大。高氧暴露(18%)和内毒素治疗(26%)均增加肺组织匀浆GSH含量，这与HMPAO摄取密切相关。24小时后，两种处理对KF均无影响。脂多糖治疗的大鼠看起来很健康，但表现出轻度的呼吸急促、BAL和炎症的组织学证据，并增加了肺湿重和干重。这些结果表明，HMPAO作为一种检测ALI的工具，在可能显示出最少的临床损伤证据的阶段具有潜在的实用价值。
99mTc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a pre-clinical marker of lung injury in two well-established rat models of human acute lung injury (ALI). Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 hours later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf). For hyperoxia rats, HMPAO lung uptake increased after 24 hours (134%) and 48 hours (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 hours after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 hours. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.