吸入偏二甲基肼和四氧化二氮引起急性肺损伤及氧化过氧化在其发生机制中的作用

Experimental study of lung injury induced by exposure to rocket liquid propellant

目的 研究吸入大剂量火箭液体推进剂偏二甲基肼 (UDMH)和四氧化二氮 (N2 O4)引起急性肺损伤 (ALI)的表现以及抗氧化系统酶与过氧化损伤在其中的作用。方法 静式染毒柜中UDMH和N2 O4浓度分别为 4 0 0ppm和 5 0ppm。受实验大鼠自主呼吸 ,染毒时间均为 10min ,在毒物暴露前及暴露后的 2、6、12、2 4、4 8h分别处死 14只动物。测定大鼠肺组织湿 /干重比 (W /D)、支气管肺泡灌洗液 (BALF)总蛋白和乳酸脱氢酶 (LDH)等肺损伤指标以及肺组织超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)、丙二醛 (MDA)和血浆MDA等抗氧化系统酶和脂质过氧化指标。观察动物一般情况及组织病理学变化。结果 大剂量UDMH和N2 O4吸入后 ,肺组织W/D、BALF蛋白和LDH均有不同程度增加 ;肺组织SOD、GSH -Px和MDA等有不同程度降低 ,血浆MDA明显升高。其峰值多出现在吸入后 6～ 12h。肺组织W/D与肺组织SOD和GSH -Px活性之间均有显著的负相关 ,相关系数r分别等于 - 0 .6 0 4 (P <0 .0 1)和 - 0 .6 4 9(P <0 .0 1)。结论 大剂量UDMH和N2 O4吸入可引起ALI,其原因可能与该物质破坏机体的抗氧化系统酶 ,造成机体过氧化损伤有关。

ObjectiveTo investigate the manifestation and the mechanisms of the acute lung injury(ALI) caused by acute exposure to mass concentration rocket liquid propellant:unsymmetrical dimethylhydrazine (UDMH) and dinitrogen tetroxide (N 2O 4). MethodsExperimental rats were exposed to UDMH 400ppm for ten minutes and N 2O 4 50ppm for ten minutes. After the exposure, 14 rats were killed on the time of 2, 6, 12, 24, 48 hours respectively. The 14 rats were as control group. The wet to dry ratio (W/D)of lung tissue, the lactic dehydrogenase (LDH) and total protein in bronchoalveolar lavage fluid (BALF), the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in lung tissue, and the MDA of plasma were measured. Histopathology was observed. ResultsThe W/D of lung tissue, the LDH and total protein in BALF were increased after the exposure to UDMH and N 2O 4, while the SOD, GSH-Px, MDA in lung tissue were decreased, and the MDA of plasma increased. The peak values of above index were presented in 6-12 hours after the exposure. The lung W/D were related to the activities of SOD and GSH-Px in lung tissue, and the correlation coefficient were -0.604(P<0.01) and -0.649(P<0.01) respectively. ConclusionExposure to UDMH and N 2O 4 on mass concentration can induce ALI, which mechanisms may be concerned with the imbalance of oxidation and anti-oxidation.