Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA.
Toxicol Appl Pharmacol. 2012 Sep 1;263(2):251-8. doi: 10.1016/j.taap.2012.06.017. Epub 2012 Jul 2.
Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228-270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery.
氯气是一种剧毒的呼吸道刺激性物质，吸入后会导致上皮细胞损伤、肺泡毛细血管屏障破坏、气道高反应性、炎症和肺水肿。氯气被认为是一种化学威胁剂，其通过意外或故意释放有可能导致急性肺损伤的大量人员伤亡。4 型磷酸二酯酶抑制剂罗利普兰被研究作为氯气诱导的肺损伤的抢救治疗方法。罗利普兰抑制细胞内信号分子环磷酸腺苷的降解。增加环磷酸腺苷水平的潜在有益效果包括抑制肺水肿、炎症和气道高反应性。将小鼠暴露于氯气（全身暴露，228-270 ppm 1 小时），并在暴露后 1 小时开始通过腹膜内、鼻内或肌肉内（水性或纳米乳液制剂）给药给予罗利普兰。腹膜内或鼻内给予罗利普兰可抑制氯气诱导的肺水肿。在灌洗液 IgM（指示血浆蛋白渗漏）、KC（Cxcl1，中性粒细胞趋化因子）和中性粒细胞方面观察到较小或没有影响。所有给药途径均抑制暴露后 1 天评估的氯气诱导的气道高反应性。该研究结果表明，罗利普兰可能是氯气诱导的肺损伤的有效抢救治疗方法，全身和靶向给药到呼吸道都是有效的给药途径。
