Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia-reperfusion through Adenosine 5'-monophosphate-activated protein kinase-sirtuin1 pathway.
BACKGROUND
Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia-reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5'-monophosphate-activated protein kinase-sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway.


METHODS
Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis.


RESULTS
Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1β), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs.


CONCLUSIONS
Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R-induced ALI.
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Huirong
H
Jing
Department of Pharmacology, Dalian Medical University, Dalian, China.
Jihong
J
Yao
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Xingming
X
Liu
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Hui
H
Fan
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Feng
F
Zhang
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Zhenlu
Z
Li
Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address: txfdl@hotmail.com.
Xiaofeng
X
Tian
Department of Nutrition, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address: zydy2ynutrition@126.com.
Yun
Y
Zhou
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D056564:Sirtuin 1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1
AMPK/SIRT1; Fish oil; Intestinal ischemia–reperfusion; Lung injury; Macrophage; ω-3 PUFAs