title: Recombinant adiponectin ameliorates liver ischemia reperfusion injury via activating the AMPK/eNOS pathway.
abstract: BACKGROUND
  It is of importance to minimize ischemia reperfusion (I/R) injury during liver operations. Reducing the inflammatory reaction is an effective way to achieve this goal. Notably, adiponectin (APN) was found to have anti-inflammatory activity in heart and renal I/R injury. Herein, we investigated the role of APN in liver I/R injury.
  
  
  METHODS
  WISTAR RATS WERE RANDOMIZED TO FOUR GROUPS: (1) sham group; (2) I/R control group; (3) I/R+APN group; and (4) I/R+APN+AMPK inhibitor group. Liver and blood samples were collected 6h and 24h after reperfusion. Liver function and histopathologic changes were assessed. Macrophage and neutrophil infiltration was detected by immunohistochemistry staining, while pro-inflammatory cytokines and chemokines released in the liver were measured using ELISA and RT-PCR, respectively. Apoptosis was analyzed by TUNEL staining and caspase-3 expression in the liver. Downstream molecules of APN were investigated by Western blotting.
  
  
  RESULTS
  Circulatory APN was down-regulated during liver I/R. When exogenous APN treatment was administered during liver I/R, alanine transaminase (ALT) and aspartate aminotransferase (AST) were decreased, and less hepatocyte necrosis was observed. Less inflammatory cell infiltration and pro-inflammatory cytokines/chemokines release were also observed in the I/R+APN group when compared with the I/R control group. APN treatment also reduced hepatocyte apoptosis, evidenced by reduced TUNEL positive cells and less caspase-3 expression in the reperfused liver. Finally, the AMPK/eNOS pathway was found to be activated by APN, and administration of an AMPK inhibitor reversed the beneficial effects of APN.
  
  
  CONCLUSIONS
  APN can protect the liver from I/R injury by reducing the inflammatory response and hepatocyte apoptosis, a process that likely involves the AMPK/eNOS pathway. The current study provides a potential pharmacologic target for liver I/R injury.
authors.affiliation: Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chuanzhao
authors.initials: C
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Maogen
authors.initials: M
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ronghai
authors.initials: R
authors.lastname: Deng
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wu
authors.forename: Anli
authors.initials: A
authors.lastname: Yang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Dongping
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: He
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052242:Adiponectin; D018925:Chemokines; D011994:Recombinant Proteins; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases