二甲双胍对LPS诱导小鼠急性肺损伤的保护作用  

Protective effect of metformin against LPS-induced acute lung injury in mice

作　　者：王贵佐[1] 韩冬 张薇[1] 张叶钦 王少纯 张永红[2] WANG Guizuo;HAN Dong;ZHANG Wei;ZHANG Yeqin;WANG Shaochun;ZHANG Yonghong(Department of Respiratory and Critical Care Medicine,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Respiratory and Critical Care Medicine,Second Affiliated Hospital of Medical College,Xi’an Jiaotong University)

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

出　　处：《山西医科大学学报》2019年第9期1267-1271,共5页Journal of Shanxi Medical University

基　　金：陕西省自然科学基金资助项目(2018JM7078)

摘　　要：目的 探讨AMPK激动剂二甲双胍对脂多糖(LPS)诱导的小鼠急性肺损伤的保护作用及可能的机制。方法 6-8周雄性BALB/c小鼠15只随机分为3组:对照组(气管内滴注无菌PBS 60 μl),LPS模型组(LPS组,气管内滴注1 mg/ml LPS 60 μl,作用24 h),二甲双胍治疗组(Met+LPS组,于滴注LPS前30 min腹腔注射二甲双胍250 mg/kg,再气管内滴注LPS作用24 h)。观察小鼠肺组织病理学改变,肺泡灌洗液中细胞总数及中性粒性细胞数变化,测定肺组织内髓过氧化物酶(MPO)活性。Western blot法检测肺组织中AMPK、P-AMPK(Thr172)及PGC1α表达的变化。结果 与对照组比较,LPS模型组小鼠组织病理学显示,肺泡壁结构明显破坏,炎性细胞浸润及组织出血增加,肺泡灌洗液中细胞总数及中性粒细胞比例明显增高( P <0.01),肺组织内MPO活性显著升高( P <0.01),PGC1α表达减少( P <0.01),P-AMPK(Thr172)水平下降。与LPS模型组比较,二甲双胍治疗组小鼠肺泡壁破坏减轻,炎性细胞浸润及组织出血减轻,髓过氧化物酶活性下降( P <0.01),P-AMPK水平( P <0.01)及PGC1α( P <0.05)的表达明显增加。结论 本研究提示AMPK激动剂二甲双胍对LPS诱导急性肺损伤具有一定保护作用,这种保护作用可能与PGC1α上调有关。Objective To investigate the protective effect of metformin against lipopolysaccharide(LPS)-induced acute lung injury in mice and its possible mechanism. Methods Fifteen male BALB/c mice(6-8 week old) were randomized divided into three groups. The mice in control group were intratracheally instilled with 60 μl of sterile PBS. The mice in LPS model group were intratracheally instilled with 60 μl of LPS (1 mg/ml) for 24 h. The mice in metformin group were intraperitoneally injected with metformin(250 mg/kg) 30 min before intratracheal treatment of LPS. After administration of LPS for 24 h, histopathological changes of lung tissue, the numbers of total cells and neutrophils in bronchoalveolar lavage fluid(BALF) and the activity of myeloperoxidase(MPO) in lung tissues in each group were observed. The expression of T-AMPK, P-AMPK(Thr172) and PGC1α in lung tissues was detected by Western blot. Results Compared with control group, the destruction of alveolar wall structure of mice, the infiltration of inflammatory cells, and hemorrhage were more obvious in LPS group.Compared with control group, the numbers of total cells and neutrophils, and the activity of MPO in lung tissues increased significantly in LPS group( P <0.01). Compared with control group, the expression of PGC1α and the level of P-AMPK (Thr172) were decreased in LPS group( P <0.01). Compared with LPS model group, the damage of alveolar wall structure in mice, inflammatory cell infiltration and tissue hemorrhage induced by LPS were inhibited in metformin group. Compared with LPS model group, the activity of MPO was decreased in metformin group( P <0.01), while the level of P-AMPK( P <0.01)and the expression of PGC1α( P <0.05)were increased significantly. Conclusion AMPK agonist metformin has a protective effect against LPS-induced acute lung injury, which may be related to the up-regulation of PGC1α.

关 键 词：二甲双胍 脂多糖 急性肺损伤 AMPK PGC1α 

分 类 号：R563[医药卫生—呼吸系统]