光气是一种重要化工原料，也是日本遗留下来的主要化武武器。我国光气中毒事故经常发生，能引起中毒性肺水肿，严重者窒息死亡，但光气中毒没有特效治疗方法。因此，光气防治是我国亟待解决的公共卫生问题。我们团队近20年研究发现主要的中毒机制，如氧化损伤、肺泡II型细胞损伤等，但针对这些机制进行的治疗研究没有突破性进展。追踪文献发现，在急性肺损伤和高原肺水肿，α1-AT基因表达升高，而肺上皮细胞α1-AT又受HNF-1的调控。我们实验发现，光气中毒性肺水肿大鼠肺脏上皮细胞α1-AT蛋白表达下调，给予α1-AT可以明显改善光气对肺脏的损伤作用。为揭示α1-AT可能是光气中毒性肺水肿发生的关键分子，本课题利用国际先进的鼻吸入染毒设备复制光气染毒大鼠肺水肿模型，从分子、细胞和动物水平，研究α1-AT及其调控因子HNF-1在光气诱导的肺水肿中的作用，为阐明光气中毒性肺水肿机制、探索其早期诊断和有效治疗提供基础。

Phosgene is a main chemical material and a main chemical warfare abandoned by Japanese in our country. The accident of phosgene happened often. People suffered from pulmonary edema and even death after they exposed to phosgene, but no specific treatment was used for pulmonary edema. Therefore, prevention and treatment for it are an important public problem to deal with in our country. Our team found several main mechanisms about phosgene-induced pulmonary edema past 20 years, such as oxidative injury, injury of alveoli type II cell and so on. But we make no breakthrough based on our mechanisms. The reports showed that over-expression of α1-antitrypsin was found in acute lung injury and pulmonary edema induced by plateau, and α1-antitrypsin was regulated by HNF-1 in pulmonary epithelial cells. Our results showed that expression of α1-antitrypsin reduced in pulmonary epithelial cells in pulmonary edema rat exposed to phosgene. Lung injury can be alleviated withα1-antitrypsin treatment. To investigate the effect of α1-AT as a key molecular in phosgene-induced pulmonary edema, this project will study on the effect of α1-AT and its regulation factor HNF-1 on toxic pulmonary edema in molecular, cell and animal level by nose-inhalation chamber. We hope to find a target molecular and new mechanism, thus pave way for the discovery of biomarker for diagnosis in early phase and specific treatment of toxic pulmonary edema induced by phosgene.