McClintock Shannon D, Hoesel Laszlo M, Das Salil K, Till Gerd O, Neff Thomas, Kunkel Robin G, Smith Milton G, Ward Peter A
The University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA.
J Appl Toxicol. 2006 Mar-Apr;26(2):126-31. doi: 10.1002/jat.1115.
Airway instillation into rats of 2-chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co-instillation with CEES of liposomes containing pegylated (PEG)-catalase (CAT), PEG-superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co-instillation of liposomes containing the reducing agents, N-acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti-oxidant compounds maximally attenuated CEES-induced lung injury by nearly 80%. Delayed airway instillation of anti-oxidant-containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes.
将硫芥化合物的半分子 2-氯乙基乙硫醚（CEES）经气道滴注到大鼠体内，会导致急性肺损伤，这可通过血浆白蛋白漏入肺内来衡量。在形态学上，肺的早期变化包括肺泡出血、纤维蛋白沉积以及中性粒细胞的流入。肺与 CEES 接触后，肺内胶原逐渐积累，随后实质塌陷。将含有聚乙二醇化（PEG）-过氧化氢酶（CAT）、PEG-超氧化物歧化酶（SOD）或二者组合的脂质体与 CEES 共同滴注，可大大减轻肺损伤的发展。同样，将含有还原剂 N-乙酰半胱氨酸（NAC）、谷胱甘肽（GSH）或白藜芦醇（RES）的脂质体共同滴注，可显著减轻急性肺损伤。补体耗竭与含有抗氧化化合物的脂质体气道滴注相结合，可最大程度减轻 CEES 诱导的肺损伤，减轻幅度近 80%。即使在肺暴露于 CEES 后 1 小时才延迟滴注含有抗氧化剂的脂质体（含有 NAC 或 GSH 或二者组合），也能显著减轻肺损伤。这些数据表明，通过脂质体递送还原剂或抗氧化酶可显著减轻 CEES 诱导的大鼠肺损伤。
