title: RhGH attenuates ischemia injury of intrahepatic bile ducts relating to liver transplantation.
abstract: BACKGROUND
  To study the effect of rhGH administration on intrahepatic cholangiocytes relating to liver transplantation with ischemia of hepatic artery, and ultimately, clarify pathologic mechanism of the injury.
  
  
  METHODS
  Rat orthotopic autologous liver transplantation was performed first. Three hours later, the rats were grouped as followed: HAL (hepatic artery ligation) group; HAL + rhGH (hepatic artery ligation followed by rhGH administration) group; CON (without hepatic artery ligation) group. Specimen was collected after 7 d. ALT and ALP of serum were measured. The pathologic changes of bile ducts of liver tissue were observed. The number of bile ducts and blood vessels in portal area were counted. Immunochemistry for VEGF, VEGFR-2, VEGFR-3, GHR, and IGF-1R of intrahepatic cholangiocytes was performed. Cholangiocytes apoptosis was evaluated by TUNEL analysis. Cholangiocytes proliferation was evaluated by PCNA immunolabeling.
  
  
  RESULTS
  ALT and ALP of HAL + rhGH group were significantly ameliorated compared with untreated animals (P < 0.05). ALT and ALP of HAL group were significantly higher compared with CON group (P < 0.05). In HAL group, the main injury of bile ducts was not reversible, whereas it was reversible in CON and rhGH groups. In HAL group, the number of bile ducts in portal area decreased, while the number of bile ducts not accompanying blood vessels increased (P < 0.05). In rhGH group, the number of bile ducts in portal area increased, while the number of bile ducts accompanying blood vessels increased compared with HAL group (P < 0.05). The expression of VEGF, VEGFR-2, VEGFR-3, GHR, and IGF-1R was significantly lower in HAL group than in CON group (P < 0.05). Following administration of rhGH to HAL rats, the expression of VEGF, VEGFR-2, VEGFR-3, IGF-1R, and GHR was significantly higher (P < 0.05). Administration of rhGH prevented increase in cholangiocytes apoptosis induced by HAL (P < 0.05). Administration of rhGH promoted increase in cholangiocytes proliferation held by HAL (P < 0.05).
  
  
  CONCLUSIONS
  Administration of rhGH appears to attenuate ischemia injury of intrahepatic bile ducts relating to liver transplantation. This function is partly related to the capacity that rhGH inhibits the apoptosis of intrahepatic cholangiocytes and prompts the proliferation and angiogenesis by increasing the expression of VEGF, VEGFR2, VEGFR3, GHR, and IGF1-R.
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Lin
authors.forename: Xianghong
authors.initials: X
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000097:blood; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology*; D006499:Hepatic Artery / Q000502:physiology; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013006:Growth Hormone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017526:Receptor, IGF Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3