Protective effects of reduced glutathione on lung injury induced by N2O4 in mice
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摘要: 目的:探讨还原型谷胱甘肽（GSH）对四氧化二氮（N2O4）吸入致小鼠肺损伤的防护作用。方法:动物模型采取在120 L静式染毒柜内吸入N2O4的方法制作。雄性ICR小鼠64只,随机分为对照组,染毒组,GSH低、中、高剂量干预组（GSH低、中、高剂量+染毒）,共五组,对照组8只,其余每组14只。染毒前,干预组分别灌胃GSH（1.25、2.50、3.75 g/kg bw·d）,对照组和染毒组灌胃等体积生理盐水,连续7 d,第7 d灌胃1 h后染毒。脱臼处死动物,检测肺组织SOD、GSH-Px活性和MDA含量,观察肺病理改变。结果:与对照组比较,染毒组肺组织SOD、GSH-Px活性和MDA含量均极显著降低（p<0.01）;与染毒组比较,GSH低、中剂量干预组肺组织SOD和GSH-Px活性均极显著提高（p<0.01）,GSH低剂量干预组MDA含量极显著提高（p<0.01）,GSH中剂量干预组MDA含量显著提高（p<0.05）。病理切片显示,GSH干预组比染毒组肺损伤程度轻。结论:GSH对N2O4吸入致小鼠肺损伤具有显著防护作用,其作用机制可能与其抑制氧化损伤有关。Abstract: Objective: To study the protective effects of reduced glutathione( GSH) on the lung injury induced by N2O4 inhalation in mice.Methods: The mice lung injury model was established through exposing 64 mice to N2O4 in a 120 L sealed cabinet. Sixty- four ICR male mice were randomly divided into five groups: the control group,the N2O4 group,the low,medium and high dose GSH- treated groups,8 mice in control group,14 mice in the other groups.1.25,2.50 and 3.75 g / kg bw·d GSH were ig administered to mice in GSH- treated groups respectively for7 days before poisoning,equal volume of normal saline for control group and N2O4 group.The GSH- treated groups and the N2O4 group were exposed to N2O4 in the cabinet 1 hour after ig administration on 7 th day.The mice were killed by dislocation,and the activities of SOD and GSH- Px and the content of MDA in lung tissue were measured,and the pathology change of lung tissue was examined. Results: Compared with the control group,the SOD,GSH- Px activities and MDA content in lung tissue of N2O4 group were significantly decreased( p < 0.01).Compared with the N2O4 group,the SOD and GSH- Px activities in lung tissue of low and medium dose GSH-treated groups were significantly increased( p < 0.01),the MDA content in lung tissue of low dose GSH- treated groups was significantly increased( p < 0.01),the MDA content in lung tissue of medium dose GSH- treated groups was increased( p < 0.05).The pathology change of lung tissue showed that the injury in low dose GSH group was lighter than that in N2O4 group.Conclusion: GSH has remarkably protective effects against the lung injury induced by N2O4 inhalation in mice,and the mechanism may be related to its inhibitory effect against oxidative damage.
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