N-乙酰半胱氨酸对偏二甲基肼和四氧化二氮吸入性肺损伤的保护作用

目的观察N-乙酰半胱氨酸(NAC)对大剂量火箭液体推进剂偏二甲基肼(UDMH)和四氧化二氮(N2O4)吸入性急性肺损伤(ALI)的保护性作用.方法42只大鼠随机平均分为对照组、毒物暴露组(暴露组)和毒物暴露+NAC治疗组(NAC干预组).制模动物在静式染毒柜中染毒,UDMH和N2O4质量浓度分别为0.98 mg/L和0.19 mg/L,均染毒10 min.NAC干预组染毒后立即经尾静脉注射NAC150 mg/kg,3 h后再次补充50 mg/kg NAC腹腔注射;另两组均以等量生理盐水代替.各组动物均于实验后6 h测定肺组织湿/干质量比(W/D)、支气管肺泡灌洗液(BALF)蛋白含量和乳酸脱氢酶(LDH)活性、肺组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和血浆丙二醛(MDA),并观察动物一般情况及组织病理学变化.结果与对照组相比,暴露组大鼠肺W/D、BALF中蛋白和LDH以及血浆MDA等均明显增加,而肺组织SOD、GSH-Px活性则明显降低;NAC干预组上述指标均有不同程度改善.暴露组大鼠有明显憋喘症状,病理学表现为明显的肺泡内渗出和肺间质水肿;而NAC干预组上述改变明显减轻.肺W/D与肺组织SOD和GSH-Px活性均呈显著负相关,相关系数r分别为-0.662和-0.707(P均＜0.01).结论NAC对大剂量UDMH和N2O4吸入性ALI有保护性治疗作用,其作用机制可能与其抗氧化和防治脂质过氧化损伤有关.

Protective effect of N - acetylcysteine on acute lung injury caused by exposure to rocket liquid propellant

OBJECTIVE: To investigate the protective effect and its mechanisms of N-acetylcysteine (NAC) on acute lung injury (ALI) caused by exposure to high concentration rocket liquid propellants asymmetrical dimethylhydrazine (UDMH) and dinitrogen tetroxide (N(2)O(4)). METHODS: Forty-two rats were randomly divided into three groups: the control group, the exposure group and the exposure plus the treatment group (NAC group). The rats of the latter two groups were exposed to UDMH 0.98 mg/L for 10 minutes and then N(2)O(4) 0.19 mg/L for another 10 minutes. After the exposure, the NAC group rats received immediately 150 mg/kg of NAC intravenously, and rein forced by intraperitoneal injection of NAC with a dose of 50 mg/kg 3 hours after the intravenous injection. The rats of other group were treated with saline in equal volume. All rats were killed after 6 hours. The lung wet to dry ratio (W/D ), the contents of lactate dehydrogenase (LDH) and total protein in bronchoalveolar lavage fluid (BALF), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue, and the malondialdehyde (MDA) of plasma were measured. Pathological examination was performed. RESULTS: The lung W/D ratio, the LDH and total protein in BALF, and the MDA of plasma were increased in the exposure group, while the activities of SOD and GSH-Px in lung tissue were decreased. The histopathology of the rats of exposure groups showed that there was exudation within alveolar spaces and prominant interstitial thickening of septa. In the NAC group, the values of the above findings were lowered, and the degree of lung injury was alleviated in histopathology. The lung W/D were negatively correlated with the activities of SOD and GSH-Px in lung tissue, and the correlation coefficient were-0662 (P<0.01) and -0707(P<0.01) respectively. CONCLUSION: The administration of NAC appears to attenuate the injury to the lung after an exposure to UDMH and N(2)O(4) in high concentration, and the antioxidant activity of NAC may be responsible for the protective effect.