二甲双胍对小鼠急性肺损伤的保护作用及可能机制研究  

Research on protective effect and possible mechanism of metformin on acute lung injury in mice

作　　者：王贵佐[1] 韩冬 马惠辉 尚文丽[1] 张薇[1] 张永红[2] WANG Gui-Zuo;HAN Dong;MA Hui-Hui;SHANG Wen-Li;ZHANG Wei;ZHANG Yong-Hong(Department of Respiratory and Critical Care Medicine,Shaanxi Provincial People′s Hospital,Xi′an 710068,China)

机构地区：[1]陕西省人民医院呼吸与危重症医学科,西安710068 [2]西安交通大学第二附属医院呼吸与危重医学科,西安710068

出　　处：《中国免疫学杂志》2020年第8期919-922,共4页Chinese Journal of Immunology

基　　金：陕西省自然科学基金(2018JM7078)资助项目。

摘　　要：目的:探讨二甲双胍对脂多糖(LPS)诱导的小鼠急性肺损伤的保护作用及可能的机制。方法:体重20~25 g的小鼠15只随机分3组:①对照组(Con):气管内滴注PBS;②LPS模型组(LPS):气管内滴注1 mg/ml LPS 60μl,作用24 h;③二甲双胍治疗组(Met+LPS):于滴注LPS前0.5 h给予二甲双胍(250 mg/kg)腹腔注射,再气管内滴注LPS作用24 h;观察各组小鼠肺组织病理学变化,肺泡灌洗液中细胞总数及中性粒细胞比例变化,测定肺组织匀浆内丙二醛(MDA)含量和SOD活力变化。Western blot方法检测肺组织中SOD1变化。结果:在LPS刺激的小鼠模型中,肺泡灌洗液中细胞总数及中性粒细胞比例明显增高,肺组织内MDA含量显著升高,SOD活力明显降低。而以二甲双胍预处理小鼠可明显抑制LPS诱发的上述变化,同时二甲双胍预处理小鼠肺组织SOD1的表达明显增加。结论:二甲双胍可对LPS诱导的急性肺损伤发挥保护作用,这种保护作用可能与上调SOD1的表达有关。Objective:To investigate the protective effect and possible mechanism of metformin on lipopolysaccharide(LPS)-induced acute lung injury in mice.Methods:Fifteen male BALB/c mice(20-25 g)were randomized divided into three groups.60μl of sterile PBS was instilled intratracheally(i.t.)to the control group.Model of acute lung injury was treated with 60μl of LPS(1 mg/ml)(i.t.)for 24 h.Mice of the third group were prior treated with metformin(250 mg/kg)by intraperitoneal injection at 0.5 h before stimulation with LPS for 24 h.After administration of LPS 24 h,histopathological changes of lung tissue,the numbers of total cells and neutrophils in bronchoalveolar lavage fluid(BALF)in each group were observed.The concentration of malondialdehyde(MDA)and activity of SOD in lung tissue were measured.The expression of SOD1 in lung tissue was detected by Western blot.Results:In the LPS treated mice,the ratio of total cells and neutrophils,the concentration of MDA in lung tissue were increased significantly;these were accompanied by the decreased activity of SOD.However,prior administration of metformin inhibited LPS induced molecular and morphological changes of acute lung injury in mice.The expression of SOD1 were induced notably in metformin treated group.Conclusion:Metformin protects LPS-induced acute lung injury,which may be related to up-regulation of expression of SOD1.

关 键 词：二甲双胍 SOD1 SOD 急性肺损伤 

分 类 号：R563[医药卫生—呼吸系统]