title: Vascular endothelial growth factor improves liver regeneration and survival after 90% hepatectomy in a rat model of diet-induced steatosis.
abstract: OBJECTIVE
  Fatty liver disease increases the risk in major liver resection for patients. As previous studies suggested that vascular endothelial growth factor (VEGF) and erythropoietin (EPO) might improve liver regeneration in nonobese animals, we investigated their effect after subtotal hepatectomy (SH) in rats with diet-induced steatosis.
  
  
  METHODS
  Male Wistar rats were fed with fatty liver-inducing diet (FLD) or normal diet (control) for 11-12 weeks followed by 90% SH. Animals were treated either with EPO, VEGF or NaCl on postoperative days 0, 1 and 3 and sacrificed 24 h or 7 days after SH. Survival rate, liver regeneration and biochemical markers were assessed. Expression of inflammatory cytokines (TNF-α, IL-6) and apoptosis-related genes (PUMA, Bcl-2) was measured by qRT-PCR.
  
  
  RESULTS
  Seven-day survival after SH was significantly decreased in the FLD group compared to controls (50 vs. 100%, p < 0.05). In FLD animals, treatment with VEGF increased 7-day survival to 90% compared to only 40% in the EPO group. After surgery, blood glucose levels of VEGF but not EPO- or NaCl-treated animals remained normal. Inflammatory genes were markedly upregulated in the EPO group 24 h after SH.
  
  
  CONCLUSIONS
  Steatosis severely impairs survival and regeneration after extensive liver resection, which can be counteracted at least in part by perioperative treatment with VEGF.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Gu
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D015870:Gene Expression / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D006498:Hepatectomy; D015850:Interleukin-6 / Q000235:genetics; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin