Role of vascular endothelial growth factor in protection of intrahepatic cholangiocytes mediated by hypoxic preconditioning after liver transplantation in rats.
OBJECTIVE
To investigate the effect on intrahepatic cholangiocytes mediated by hypoxic preconditioning (HP) after liver transplantation and the role of vascular endothelial growth factor (VEGF).


METHODS
This experiment was based on a model of rat orthotopic liver autotransplantation. Sprague-Dawley rats were randomly divided into 3 groups: normal control, autotransplantation (AT), and HP. The HP group was subjected to 8% oxygen atmosphere for 90 minutes before surgery. At 6, 12, 24, and 48 hours after autotransplantation, the rats were killed for testing .Serum total bilirubin, direct bilirubin, and alkaline phosphatase concentrations were determined. The microstructure of cholangiocytes and the ultramicrostructure of cholangioles were determined. Immunohistochemistry was used to detect the expression of VEGF and the proliferation rate of cholangiocytes.


RESULTS
Total bilirubin, direct bilirubin, and alkaline phosphatase concentrations in the AT group increased considerably more than in the HP group during the entire interval (P < .05). Light microscopy demonstrated that the microstructure of cholangiocytes in the AT group was damaged more seriously than in the HP group. At transmission electron microscopy, the ultramicrostructure of cholangioles was changed more obviously than in the HP group. The expression of VEGF on cholangiocytes and the proliferation rate of cholangiocytes were higher in the HP group than in the AT group over the entire experiment (P < .05).


CONCLUSIONS
Hypoxic preconditioning has a protective effect on cholangiocytes after liver autotransplantation. The mechanism may be related to HP-induced overexpression of VEGF on cholangiocytes.
Zhou
B
B
Institute of General Surgical Research, Second Affiliated Hospital, Yangzhou University, China.
Zhang
P-J
PJ
Tian
T
T
Jin
C
C
Li
Y
Y
Feng
M
M
Liu
X-Y
XY
Jie
L
L
Tao
L-D
LD
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000502:physiology; D001659:Biliary Tract / Q000187:drug effects / Q000502:physiology; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D000469:Alkaline Phosphatase; D001663:Bilirubin