Activation of AMPK attenuates LPS-induced acute lung injury by upregulation of PGC1 and SOD1

被引：46

作者：

Wang, Guizuo ^{[1
]}

Song, Yang ^{[1
]}

Feng, Wei ^{[1
]}

Liu, Lu ^{[1
]}

Zhu, Yanting ^{[1
]}

Xie, Xinming ^{[1
]}

Pan, Yilin ^{[1
]}

Ke, Rui ^{[1
]}

Li, Shaojun ^{[1
]}

Li, Fangwei ^{[1
]}

Yang, Lan ^{[1
]}

Li, Manxiang ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Resp Internal Med, Coll Med, Xian 710061, Shanxi, Peoples R China

来源：

EXPERIMENTAL AND THERAPEUTIC MEDICINE | 2016年 / 12卷 / 03期

基金：

中国国家自然科学基金;

关键词：

acute lung injury; AMP-activated protein kinase; peroxisome proliferator-activated receptor coactivator 1; superoxide dismutase 1; OXIDATIVE STRESS; METFORMIN; DISEASES; CELLS; COACTIVATORS; PREVENTS;

D O I：

10.3892/etm.2016.3465

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Evidence suggests that an imbalance between oxidation and antioxidation is involved in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Activation of AMP-activated protein kinase (AMPK) has been shown to inhibit the occurrence of ALI/ARDS. However, it is unknown whether activation of AMPK benefits ALI/ARDS by restoration of the oxidant and antioxidant balance, and which mechanisms are responsible for this process. The present study aimed to address these issues. Lipopolysaccharide (LPS) induced pronounced pathological changes of ALI in mice; these were accompanied by elevated production of malondialdehyde (MDA) and decreased activity of superoxide dismutase (SOD) compared with control mice. Prior treatment of mice with the AMPK agonist metformin significantly suppressed the LPS-induced development of ALI, reduced the elevation of MDA and increased the activity of SOD. Further analysis indicated that activation of AMPK also stimulated the protein expression of peroxisome proliferator-activated receptor coactivator 1 (PGC1) and superoxide dismutase 1 (SOD1). This study suggests that activation of AMPK by metformin inhibits oxidative stress by upregulation of PGC1 and SOD1, thereby suppressing the development of ALI/ARDS, and has potential value in the clinical treatment of such conditions.

引用

页码：1551 / 1555

页数：5

共 22 条

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