In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin.
In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin.
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DOI：
10.1016/j.nucmedbio.2014.08.010
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发表时间：
2015-01
影响因子：
3.1
通讯作者：
Clough AV
中科院分区：
文献类型：
--
作者：
Audi SH;Jacobs ER;Zhao M;Roerig DL;Haworth ST;Clough AV
99 mTc-duramycin，DU，是识别细胞死亡的组织损伤的SPECT生物标志物。本研究的目的是探讨DU成像的潜力，以量化毛细血管内皮细胞死亡的大鼠肺损伤高氧暴露作为急性肺损伤模型。将大鼠暴露于室内空气（常氧）或>98% O2 48或60小时。麻醉大鼠静脉注射DU，在稳态下采集肺造影图像，并从图像中定量肺DU摄取。死后，取出肺进行组织学研究。连续肺切片进行半胱天冬酶活化和内皮细胞和上皮细胞的免疫染色。与常氧大鼠相比，暴露48小时和60小时的大鼠肺DU摄取分别显著增加39%和146%（p < 0.001）。肺DU摄取与裂解的胱天蛋白酶3（CC 3）阳性细胞数之间存在强相关性（r2 = 0.82，p = 0.005），高氧肺中内皮细胞占CC 3阳性细胞的50%以上。组织学显示48小时内肺形态保持完好。到60小时时，有水肿和中度嗜中性粒细胞浸润的证据。在任何实质性肺损伤迹象出现之前，大鼠体内肺DU摄取在> 98%O2暴露48小时后增加。这些结果表明，凋亡的内皮细胞是增强DU肺摄取的主要贡献者，并支持DU成像用于检测体内早期内皮细胞死亡的效用。
99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Lung DU uptake increased significantly (p < 0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r2 = 0.82, p = 0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo.
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DOI：
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发表时间：
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影响因子：
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