Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
Ann N Y Acad Sci. 2020 Nov;1480(1):246-256. doi: 10.1111/nyas.14525. Epub 2020 Nov 9.
Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophage-dominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF-α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM-induced lung injury in rodents and assess the efficacy of anti-TNF-α antibody in mitigating toxicity. Anti-TNF-α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate-buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1-28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high-signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti-TNF-α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.
氮芥（NM）可导致急性肺损伤，进而进展为纤维化。这与巨噬细胞主导的炎症反应以及促炎/致纤维化介质的产生有关，包括肿瘤坏死因子-α（TNF-α）。在此，我们改进了磁共振成像（MRI）和计算机断层扫描（CT）成像方法，以追踪啮齿动物 NM 诱导的肺损伤的进展，并评估抗 TNF-α 抗体减轻毒性的效果。抗 TNF-α 抗体（15mg/kg，每 8 天静脉内注射一次）于磷酸盐缓冲盐水对照或 NM（0.125mg/kg，气管内注射）处理后 30 分钟开始给予大鼠。动物在暴露前和暴露后 1-28 天进行 MRI 和 CT 成像。通过定量高信号肺容积，我们使用 MRI 来表征急性肺损伤和纤维化，该高信号肺容积代表水肿、炎症和组织实变；这些病理学在 NM 暴露后持续 28 天。CT 扫描用于评估肺的结构成分，并记录组织密度的变化。CT 扫描显示，在对照动物中，总肺容积随时间增加。用 NM 处理大鼠导致肺容积减少；抗 TNF-α 抗体减轻了这种减少。这些研究表明，MRI 和 CT 可用于监测肺部疾病和治疗干预的效果。
