还原型谷胱甘肽对四氧化二氮致小鼠肺损伤的防护作用

Protective effects of reduced glutathione on lung injury induced by N_2O_4 in mice

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。

Objective： To study the protective effects of reduced glutathione （GSH）on the lung injury induced by N204inhalation in mice.Methods ：The mice lung injury model was established through exposing 64 mice to N204 in a 120 L sealed cabinet.Sixty-four ICR male mice were randomly divided into five groups：the control group,the N204 group,the low, medium and high dose GSH-treated groups,8 mice in control group, 14 mice in the other groups.].25,2.50 and 3.75 g/kg bw.d GSH were ig administered to mice in GSH-treated groups respectively for 7 days before poisoning,equal volume of normal saline for control group and N2O4 group.The GSH-treated groups and the N204 group were exposed to N204 in the cabinet ! 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 N204 group were significantly decreased （p 〈 0.01 ）. Compared with the N204 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 N204 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.