Qin Xu-Jun, Li Ying-Na, Liang Xin, Wang Peng, Hai Chun-Xu
Department of Toxicology, The Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, China.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):150-5. doi: 10.1016/j.bbrc.2007.12.111. Epub 2007 Dec 26.
Phosgene is a toxic gas that is widely used in modern industry, and its inhalation can cause severe pulmonary edema. There is no effective clinical treatment because the mechanism of phosgene-induced pulmonary edema still remains unclear. Many studies have demonstrated that the Na(+)/K(+)-ATPase plays a critical role in clearing pulmonary edema and the inhibition of Na(+)/K(+)-ATPase protein expression has been found in many other pulmonary edema models. In the present study, after the mice were exposed to phosgene, there was serious pulmonary edema, indicating the dysfunction of the ATPases in mice. However, in vitro enzyme study showed that there were increases in the activities of the Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Further investigation showed that the ATP content and mitochondrial respiratory control ratio (RCR) in the lungs decreased significantly. The oxidative stress product, malondialdehyde (MDA), increased while the antioxidants (GSH, SOD, and TAC) decreased significantly. These results indicate that mitochondrial respiration is the target of phosgene. The dysfunction of ATPases due to impaired mitochondrial respiration may be a new mechanism of phosgene-induced pulmonary edema.
光气是一种在现代工业中广泛使用的有毒气体，吸入光气会导致严重的肺水肿。由于光气诱导肺水肿的机制仍不清楚，目前尚无有效的临床治疗方法。许多研究表明，Na(+)/K(+)-ATP酶在清除肺水肿中起关键作用，并且在许多其他肺水肿模型中都发现了Na(+)/K(+)-ATP酶蛋白表达受到抑制。在本研究中，小鼠暴露于光气后，出现了严重的肺水肿，表明小鼠体内ATP酶功能异常。然而，体外酶学研究表明，Na(+)/K(+)-ATP酶和Ca(2+)-ATP酶的活性增加。进一步研究表明，肺组织中的ATP含量和线粒体呼吸控制率（RCR）显著降低。氧化应激产物丙二醛（MDA）增加，而抗氧化剂（GSH、SOD和TAC）显著减少。这些结果表明线粒体呼吸是光气作用的靶点。线粒体呼吸受损导致的ATP酶功能障碍可能是光气诱导肺水肿的一种新机制。
